Apparatus for the continuous separation of biological fluids into components and method of using same

ABSTRACT

The present invention provides an apparatus for separating components of a fluid having an outer housing containing a core wherein three separate fluid pathways are provided to allow continuous separation of biological fluids.

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation-in-part application of U.S.patent application Ser. No. 10/375,628, filed Feb. 27, 2003, whichclaims the benefit of U.S. Provisional Application, Serial No.60/361,287, filed Mar. 4, 2002, both of which are hereby incorporated byreference in their entireties.

TECHNICAL FIELD OF THE INVENTION

[0002] The present invention generally relates to methods and apparatusfor separating a fluid into its components, for example, a biological orsensitive fluid such as blood, and specifically to methods and apparatusthat use centrifugal force to separate a fluid into its components bydensity so as to improve the component yield.

BACKGROUND ART

[0003] With the advance of medical sciences, it has become possible totreat a patient's blood in closed-loop processes, returning thepatient's own treated blood back to him in one medical treatment. Anexample of such processes include external treatment methods fordiseases in which there is a pathological increase of lymphocytes, suchas cutaneous T-cell lymphoma or other diseases affecting white bloodcells. In such methods, the patient's blood is irradiated withultraviolet light in the presence of a chemical or an antibody.Ultraviolet light affects the bonding between the lymphocytes and thechemical or antibody that inhibits the metabolic processes of thelymphocytes.

[0004] During one of these medical treatments, a centrifuge bowl, suchas, for example, a Latham bowl, as shown in U.S. Pat. No. 4,303,193,expressly incorporated by reference in its entirety herein, separatesblood into red blood cells (“RBCs”) and buffy coat. The Latham bowl is ablood component separator that has been used for some time in themedical apheresis market as well as in innovative medical therapies suchas extracorporeal photopheresis (ECP). PCT Applications WO 97/36581 andWO 97/36634, and U.S. Pat. Nos. 4,321,919; 4,398,906; 4,428,744; and4,464,166 provide descriptions of extracorporeal photopheresis, and arehereby expressly incorporated by reference in their entirety.

[0005] The Latham bowl efficiency is often measured by the white bloodcell (“WBC”) “yield,” which is typically about 50%. Yield is defined asthe percentage of cells collected versus the number processed. Whencompared to other types of whole blood separators, this high yieldenables the Latham bowl separator to collect much larger volumes of WBCswhile processing much less whole blood from the donor patient. However,a major drawback to the Latham bowl separator is that the separationprocess must be repeatedly stopped to remove the packed RBCs and plasmaonce they fill the inside of the bowl, creating a “batch-type” process.Although the Latham bowl separator has a high volume yield, the constantfilling and emptying of this bowl wastes time; thus, the process isconsidered less efficient with respect to time. Additionally, the Lathambowl requires a rotating seal, which is expensive and difficult tomanufacture.

[0006] An additional drawback of centrifugal processing apparatus hasbeen their high cost of manufacture due to strict tolerances, rotatingseals, and extensive manufacturing processes.

DISCLOSURE OF THE INVENTION

[0007] The present invention provided an apparatus for separatingcomponents of a fluid comprising: an outer housing with an upper housingend and a lower housing end, wherein said outer housing increases indiameter from said upper housing end to said lower housing end, saidlower housing end having a housing floor and said housing upper endhaving a housing outlet, said outer housing adapted for rotation about acenter axis; said outer housing containing a core in said interiorvolume; the core having an outer wall, an upper core end, and a lowercore end; said core connected with said outer housing for rotationtherewith; and providing a separation volume between said core and saidouter housing; said core end having a lumen connector and a lumenconnector top surface; a first lumen for providing fluid communicationfrom the housing outlet through the lumen connector and then radiallyoutward through the core to the fluid separation volume; a second lumenproviding fluid communications from the housing outlet extending axiallyalong center axis to housing floor; a connection sleeve which forms withthe lumen connector a chamber and provide fluid communications betweenthe housing outlet and the separation volume.

[0008] In another embodiment of the present invention is provided amethod for separating components of a fluid into a higher densitycomponent and a lower density component comprising: providing acentrifuge bowl have a first bowl channel, a second bowl channel, and abowl chamber; flowing said fluid from a source into said centrifuge bowlthrough said first bowl channel; rotating said centrifuge bowl about anaxis; removing said higher density component from said bowl via saidsecond bowl channel; and removing said lower density component from saidbowl via said bowl chamber.

BRIEF DESCRIPTION OF THE DRAWINGS

[0009] The invention is described in detail with respect to theaccompanying drawings, which illustrate an embodiment of the inventiveapparatus, assemblies, systems, and methods.

[0010]FIG. 1 is a schematic representation of an embodiment of adisposable kit for use in photopheresis therapy embodying features ofthe present invention.

[0011]FIG. 2 is an elevated perspective view of an embodiment of acassette for controlling fluid flow in the disposable photopheresis kitof FIG. 1.

[0012]FIG. 3 is an exploded view of the cassette of FIG. 2.

[0013]FIG. 4 is a top view of the cassette of FIG. 2 with the coverremoved and showing internal tubular circuitry.

[0014]FIG. 5 is a bottom view of a cover of cassette of FIG. 2.

[0015]FIG. 6 is an elevated perspective view of an embodiment of afilter assembly.

[0016]FIG. 7 is bottom perspective view of the filter assembly of FIG.6.

[0017]FIG. 8 is an exploded view of the filter assembly of FIG. 6.

[0018]FIG. 9 is a rear perspective view of the filter assembly of FIG.6.

[0019]FIG. 10 is schematic representation of the filter assembly of FIG.6 coupled to pressure sensors and a data processor.

[0020]FIG. 11 is a front view of an irradiation chamber.

[0021]FIG. 12 is a side longitudinal view of the irradiation chamber ofFIG. 11.

[0022]FIG. 13 is a side transverse view of the irradiation chamber ofFIG. 11

[0023]FIG. 14 is a cut-away view of a section of the first plate and thesecond plate prior to being joined together to form the irradiationchamber of FIG. 11.

[0024]FIG. 15 is a cut-away dimensional end view of the irradiationchamber of FIG. 11.

[0025]FIG. 16 is a perspective view of the irradiation chamber of FIG.11 positioned within a UVA light assembly.

[0026]FIG. 17 is an elevated perspective view of an embodiment of apermanent tower system for use in conjunction with a disposable kit forfacilitating a photopheresis therapy session.

[0027]FIG. 18 is a cross-sectional view of an embodiment of thephotoactivation chamber, without a UVA light assembly, used in the towersystem of FIG. 17.

[0028]FIG. 19 is a cross-sectional view of an embodiment of thecentrifuge chamber used in the tower system of FIG. 17.

[0029]FIG. 20 is an electrical schematic of the leak detection circuitprovided in the photoactivation chamber of FIG. 18.

[0030]FIG. 21 is an electrical schematic of the leak detection circuitprovided in the centrifuge chamber of FIG. 19.

[0031]FIG. 22 is an elevated perspective view of an embodiment of thefluid flow control deck of the tower system of FIG. 17.

[0032]FIG. 23 is a perspective bottom view of the control deck of FIG.22.

[0033]FIG. 24 is an exploded view of the control deck of FIG. 22.

[0034]FIG. 25 is a top perspective view of the control deck of FIG. 22with the cassette of FIG. 2 loaded thereon.

[0035]FIG. 26 is a flowchart of an embodiment of a photopheresistreatment process.

[0036]FIG. 27 is a schematic of an embodiment of the fluid flow circuitused in performing the treatment process of FIG. 26.

[0037]FIG. 28 is top perspective view an embodiment of a peristalticpump.

[0038]FIG. 29 is a cross sectional side view of the peristaltic pump ofFIG. 28.

[0039]FIG. 30 is a top perspective view the rotor of the peristalticpump of FIG. 29.

[0040]FIG. 31 is a bottom perspective view of the rotor of FIG. 30.

[0041]FIG. 32 is a top view of the peristaltic pump of FIG. 28.

[0042]FIG. 33 is a top view of the peristaltic pump of FIG. 28 in aloading position and near the cassette of FIG. 2.

[0043]FIG. 34 is an electrical schematic of the infrared communicationport circuit.

[0044]FIG. 35 illustrates an embodiment of a centrifuge bowl and arotating frame.

[0045]FIG. 36 is a dimensional view of the bowl of FIG. 35.

[0046]FIG. 37 is an exploded view of the bowl of FIG. 36.

[0047]FIG. 38 shows a cross sectional view of the bowl of FIG. 36 alongthe line XIX-XIX.

[0048]FIG. 39A shows a cross sectional view of a connection sleeve inplace with a lumen connector of the bowl of FIG. 38 along the line XX.

[0049]FIG. 39B shows another cross sectional view of a connection sleevein place with a lumen connector of the bowl of FIG. 38.

[0050]FIG. 40 shows a cross sectional view of the top core of the bowlof FIG. 37.

[0051]FIG. 41 shows a dimensional view of the top core and upper plateof FIG. 37.

[0052]FIG. 42 shows a bottom view of the top core of FIG. 41.

[0053]FIG. 43A shows a dimensional exploded view of the bottom core anda lower plate of the bowl of FIG. 37.

[0054]FIG. 43B shows an dimensional cross section view of the bottomcore and a lower plate of the bowl of FIG. 43A attached together.

[0055]FIG. 44 shows an exploded side view of the bottom core and a lowerplate of FIG. 43A.

[0056]FIG. 45 shows a dimensional view of another embodiment of aconduit assembly.

[0057]FIG. 46 shows a dimensional view of the connection sleeve of FIG.45.

[0058]FIG. 47 shows a dimensional view of one end of conduit assembly ofFIG. 45.

[0059]FIG. 48 shows a dimensional view of an anchor end of the presentinvention.

[0060]FIG. 49 shows a lateral cross-sectional view of an anchor end.

[0061]FIG. 50 shows a horizontal cross-sectional view of an anchor endtaken along line XXI.

[0062]FIG. 51 illustrates a dimensional view of the rotating frame ofFIG. 35.

[0063]FIG. 52 is an enlarged view of a holder for an external conduit.

[0064]FIG. 53 shows an alternative embodiment of the bowl with thecross-section taken similarly to that shown in FIG. 38.

[0065]FIG. 54 shows an alternative embodiment of the top core.

[0066]FIG. 55 shows an alternative embodiment of the connection sleeve.

MODES FOR CARRYING OUT THE INVENTION

[0067] Features of the present invention are embodied in the permanentblood driving equipment, the disposable photopheresis kit, the variousdevices which make up the disposable kit, and the correspondingtreatment process. The following written description is outlined asfollows:

[0068] I. Disposable Photopheresis Kit

[0069] A. Cassette for Controlling Fluid Flow

[0070] 1. Filter Assembly

[0071] B. Irradiation Chamber

[0072] C. Centrifuge Bowl

[0073] 1. Drive Tube

[0074] II. Permanent Tower System

[0075] A Photoactivation Chamber

[0076] B. Centrifuge Chamber

[0077] C. Fluid Flow Control Deck

[0078] 1. Cassette Clamping Mechanism

[0079] 2. Self-Loading Peristaltic Pumps

[0080] D. Infra-Red Communication

[0081] III. Photopheresis Treatment Process

[0082] The above-outline is included to facilitate understanding of thefeatures of the present invention. The outline is not limiting of thepresent invention and is not intended to categorize or limit any aspectof the invention. The inventions are described and illustrated insufficient detail that those skilled in this art can readily make anduse them. However, various alternatives, modifications, and improvementsshould become readily apparent without departing from the spirit andscope of the invention. Specifically, while the invention is describedin the context of a disposable kit and permanent blood drive system foruse in photopheresis therapy, certain aspects of the invention are notso limited and are applicable to kits and systems used for renderingother therapies, such as apheresis or any other extracorporeal bloodtreatment therapy.

[0083] I. Disposable Photopheresis Kit

[0084]FIG. 1 illustrates disposable photopheresis kit 1000 embodyingfeatures of the present invention. It is necessary that a new disposablesterile kit be used for each therapy session. In order to facilitate thecirculation of fluids through photopheresis kit 1000, and to treat bloodfluids circulating therethrough, photopheresis kit 1000 is installed inpermanent tower system 2000 (FIG. 17). The installation of photopheresiskit 1000 into tower system 2000 is described in detail below.

[0085] Photopheresis kit 1000 comprises cassette 1100, centrifuge bowl10, irradiation chamber700, hematocrit sensor 1125, removable data card1195, treatment bag 50, and plasma collection bag 51. Photopheresis kit1000 further comprises saline connector spike 1190 and anticoagulantconnector spike 1191 for respectively connecting saline andanticoagulant fluid bags (not shown). Photopheresis kit 1000 has all thenecessary tubing and connectors to fluidly connect all devices and toroute the circulation of fluids during a photopheresis treatmentsession. All tubing is sterile medical grade flexible tubing. Triportconnectors 1192 are provided at various positions for the introductionof fluids into the tubing if necessary.

[0086] Needle adapters 1193 and 1194 are provided for respectivelyconnecting photopheresis kit 1000 to needles for drawing whole bloodfrom a patient and returning blood fluids to the patient. Alternatively,photopheresis kit 1000 can be adapted to use a single needle to bothdraw whole blood from the patient and return blood fluids to thepatient. However, a two needle kit is preferred because of the abilityto simultaneously draw whole blood and return blood fluids to thepatient. When a patient is hooked up to photopheresis kit 1000, a closedloop system is formed.

[0087] Cassette 1100 acts both as a tube organizer and a fluid flowrouter. Irradiation chamber 700 is used to expose blood fluids to UVlight. Centrifuge bowl 10 separates whole blood into its differentcomponents according to density. Treatment bag 50 is a 1000 mL threeport bag. Straight bond port 52 is used to inject a photoactivatable orphotosensitive compound into treatment bag 50. Plasma collection bag 51is 1000 mL two port bag. Both treatment bag 50 and plasma collection bag51 have a hinged cap spike tube 53 which can be used for drainage ifnecessary. Photopheresis kit 1000 further comprises hydrophobic filters1555 and 1556 which are adapted to connect to pressure transducers 1550and 1551 to filter 1500 via vent tubes 1552 and 1553 for monitoring andcontrolling the pressures within tubes connecting the patient (FIG. 10).Monitoring the pressure helps ensure that the kit is operating withinsafe pressure limits. The individual devices of photopheresis kit 1000,and their functioning, are discussed below in detail.

[0088] A. Cassette for Controlling Fluid Flow

[0089]FIG. 2 shows a top perspective view of a disposable cassette 1100for valving, pumping, and controlling the movement of blood fluidsduring a photopheresis treatment session. Cassette 1100 has housing 1101that forms an internal space that acts as a casing for its variousinternal components and tubular circuitry. Housing 1101 is preferablymade of hard plastic, but can be made of any suitably rigid material.Housing 1101 has side wall 1104 and top surface 1105. Side wall 1104 ofhousing 1101 has tabs 1102 and 1103 extending therefrom. During aphotopheresis treatment, cassette 1100 needs to be secured to deck 1200of tower system 2000, as is best illustrated in FIG. 25. Tabs 1102 and1103 help position and secure cassette 1100 to deck 1200.

[0090] Cassette 1100 has fluid inlet tubes 1106, 1107, 1108, 1109, 1110,1111, and 1112 for receiving fluids into cassette 1100, fluid outlettubes 1114, 1115, 1116, 1117, 1118, and 1119 for expelling fluids fromcassette 1100, and fluid inlet/outlet tube 1113 that can be used forboth introducing and expelling fluids into and out of cassette 1100.These fluid input and output tubes fluidly couple cassette 1100 to apatient being treated, as well as the various devices of photopheresiskit 1000, such as centrifuge bowl 10, irradiation chamber700, treatmentbag 50, plasma collection bag 51, and bags containing saline,anticoagulation fluid to form a closed-loop extracorporeal fluid circuit(FIG. 27).

[0091] Pump tube loops 1120, 1121, 1122, 1123, and 1124 protrude fromside wall 1104 of housing 1101. Pump tube loops 1120, 1121, 1122, 1123,and 1124 are provided for facilitating the circulation of fluidsthroughout photopheresis kit 1000 during therapy. More specifically,when cassette 1100 is secured to deck 1200 for operation, each one ofsaid pump tube loops 1120, 1121, 1122, 1123, and 1124 are loaded into acorresponding peristaltic pump 1301, 1302, 1303, 1304, and 1305 (FIG.4). Peristaltic pumps 1301, 1302, 1303, 1304, and 1305 drive fluidthrough the respective pump tube loops 1120, 1121, 1122, 1123, and 1124in a predetermined direction, thereby driving fluid throughphotopheresis kit 1000 (FIG. 1) as necessary. The operation andautomatic loading and unloading of peristaltic pumps 1301, 1302, 1303,1304, and 1305 is discussed in detail below with respect to FIGS. 28-33.

[0092] Turning now to FIG. 3, cassette 1100 is shown with housing 1101in an exploded state. For ease of illustration and description, theinternal tubular circuitry within housing 1101 is not illustrated inFIG. 3. The internal tubular circuitry is illustrated in FIG. 4 and willbe discussed in relation thereto. Cassette 1100 has filter assembly 1500positioned therein and in fluid connection with inlet tube 1106, outlettube 1114, and one end of each of pump tube loops 1120 and 1121. Filterassembly 1500 comprises vent chambers 1540 and 1542. Filter assembly1500, and its functioning, is discussed in detail below with respect toFIGS. 6-10.

[0093] Housing 1101 comprises cover 1130 and base 1131. Cover 1130 hastop surface 1105, a bottom surface 1160 (FIG. 5), and side wall 1104.Cover 1130 has openings 1132 and 1133 for allowing vent chambers 1540and 1542 of filter assembly 1500 to extend therethrough. Side wall 1104has a plurality of tube slots 1134 to allow the inlet tubes, outlettubes, and pump loop tubes to pass into the internal space of housing1101 for connection with the internal tubular circuitry located therein.Only a few tube slots 1134 are labeled in FIG. 3 to avoid numericalcrowding. Tabs 1102 and 1103 are positioned on side wall 1104 so as notto interfere with tube slots 1134. Cover 1130 has occlusion bars 1162and 1162A extending from bottom surface 1160 (FIG. 5). Occlusion bars1162 and 1162A are preferably molded into bottom surface 1160 of cover1130 during its formation.

[0094] Base 1131 has a plurality of U-shaped tube-holders 1135 extendingupward from top surface 1136. U-shaped tube holders 1135 hold the inlettubes, outlet tubes, pump loop tubes, filter assembly, and internaltubular circuitry in place. Only a few U-shaped holders 1135 are labeledin FIG. 3 to avoid numerical crowding. Preferably, a U-shaped holder1135 is provided on base 1131 at each location where an inlet tube, anoutlet tube, or a pump loop tube passes through a tube slot 1134 on sidewall 1104. Male extrusions 1136 protrude from top surface 1136 of base1131 for mating with corresponding female holes 1161 located on bottomsurface 1160 of cover 1130 (FIG. 5). Preferably, a male protrusion 1136is located at or near each of the four comers of base 1130 and nearfilter 1500. Male protrusions 1136 mate with the female holes 1161 toform a snap-fit and secure base 1131 to cover 1130.

[0095] Base 1131 further comprises a hub 1140. Hub 1140 is a five-waytube connector used to connect five tubes of the internal tubularcircuitry. Preferably, three apertures 1137 are located near andsurround three of the tubes leading into hub 1140. Hub 1140 acts as acentralized junction which can be used, in conjunction with compressionactuators 1240-1247 (FIG. 22), to direct fluids through photopheresiskit 1000 and to and from the patient. In addition to hub 1140,appropriate tube connectors, such as T-connectors 1141 and Y-connector1142, are used to obtain the desired flexible tubing pathways.

[0096] Five apertures 1137 are located on the floor of base 1130. Eachaperture 1137 is surrounded by an aperture wall 1138 having slots 1139for passing portions of the internal tubular circuitry therethrough. Anelongated aperture 1157 is also provided on the floor of base 1131.Apertures 1137 are located on base 1131 to align with correspondingcompression actuators 1243-1247 of deck 1200 (FIG. 22). Aperture 1157 islocated on base 1131 to align with compression actuators 1240-1242 ofdeck 1200 (FIG. 22). Each aperture 1137 is sized so that a singlecompression actuator 1243-1247 can extend therethrough. Aperture 1157 issized so that three compression actuators 1240-1242 can extendtherethrough. Compression actuators 1240-1247 are used to close/occludeand open certain fluid passageways of the internal tubular circuitry inorder to facilitate or prohibit fluid flow along a desired path. When itis desired to have a certain passageway open so that fluid can flowtherethrough, the compression actuator 1240-1247 for that passageway isin a lowered position However, when it is desired to have a certainfluid passageway closed so that fluid can not flow therethrough, theappropriate compression actuator 1240-1247 is raised, extending thecompression actuator 1240-1247 through aperture 1137 or 1157 andcompressing a portion of the flexible tubular circuitry against bottomsurface 1160 (FIG. 5) of cover 1130, thereby closing that passageway.Preferably, occlusion bars 1163 and 1173 (FIG. 5) are positioned onbottom surface 1160 to align with the compression actuators 1240-1247 sothat the portion of flexible tubing being occluded is compressed againstocclusion bar 1163 or 1173. Alternatively, the occlusion bar can beomitted or located on the compression actuators themselves.

[0097] It is preferable for cassette 1100 to have a unique identifierthat can communicate with and relay information to permanent towersystem 2000. The unique identifier is provided to ensure that thedisposable photopheresis kit is compatible with the blood driveequipment into which it is being loaded, and that the photopheresis kitis capable of running the desired treatment process. The uniqueidentifier can also be used as a means to ensure that the disposablephotopheresis kit is of a certain brand name or make. In the illustratedexample, the unique identifier is embodied as data card 1195 (FIG. 2)that is inserted into data card receiving port 2001 of permanent towersystem 2000 (FIG. 17). Data card 1195 has both read and writecapabilities and can store data relating to the treatment therapyperformed for future analysis. The unique identifier can also take on avariety of forms, including, for example, a microchip that interactswith the blood drive equipment when the kit is loaded, a bar code, or aserial number.

[0098] Cover 1130 has data card holder 1134 for holding data card 1195(FIG. 1). Data card holder 1134 comprises four elevated ridges in asegmented rectangular shape for receiving and holding data card 1195 tocassette 1100. Data card holder 1134 holds data card 1195 in place via asnap-fit (FIG. 2).

[0099] Referring now to FIGS. 1 and 4, the internal tubular circuitry ofcassette 1100 will now be discussed. At least a portion of the internaltubular circuitry is preferably made of flexible plastic tubing that canbe pinched shut by the exertion of pressure without compromising thehermetic integrity of the tube. Base 1131 of cassette 1100 isillustrated in FIG. 4 so that the internal tubular circuitry can beviewed. Inlet tubes 1107 and 1108 and outlet tube 1115 are provided forcoupling cassette 1100 to centrifuge bowl 10 (FIG. 1). Morespecifically, outlet tube 1115 is provide for delivering whole bloodfrom cassette 1100 to centrifuge bowl 10, and inlet tubes 1107 and 1108are respectively provide for returning a lower density blood componentsand higher density blood components to cassette 1100 for further routingthrough photopheresis kit 1000. The lower density blood components caninclude, for example, plasma, leukocytes, platelets, buffy coat, or anycombination thereof. The higher density components can include, forexample, red blood cells. Outlet tube 1117 and inlet tube 1112 fluidlycouple cassette 1100 to irradiation chamber 700. More specifically,outlet tube 1117 is provided for delivering an untreated lower densityblood component, for example buffy coat, to irradiation chamber700 forexposure to photo energy, while inlet tube 1112 is provided forreturning the treated lower density blood component to cassette 1100 forfurther routing.

[0100] Inlet tube 1111 and outlet tube 1116 couple treatment bag 50 tocassette 1100. Outlet tube 1116 is provided to deliver an untreated lowdensity blood component, for example buffy coat, to treatment bag 50.Outlet tube 1116 has hematocrit (“HCT”) sensor 1125 operably connectedthereto to monitor for the introduction of a high density bloodcomponent, such as red blood cells. HCT sensor 1125 is a photo sensorassembly and is operably coupled to a controller. HCT sensor 1125 sendsa detection signal to the controller when red blood cells are detectedin outlet tube 1116 and the controller will take the appropriate action.Inlet tube 1111 is provided to return the untreated low density bloodcomponent from treatment bag 50 to cassette 1100 for further routing.Inlet tubes 1109 and 1110 are respectively connected to a saline andanticoagulant storage bags (not shown) via spikes 1190 and 1191 and areprovided for delivering saline and an anticoagulant fluid to cassette1100 for further routing to the patient.

[0101] Inlet/Outlet tube 1113 and outlet tube 1118 couple plasmacollection bag 50 to cassette 1100. More specifically, outlet tube 1118delivers a blood component, such as plasma, to plasma collection bag 51.Inlet/Outlet tube 1113 can be used to either deliver red blood cells toplasma collection bag 51 from cassette 1100 or return the bloodcomponent(s) that build up in plasma collection bag 51 to cassette 1100for further routing. Inlet tube 1106 and outlet tubes 1119 and 1114 arecoupled to a patient. Specifically, outlet tube 1114 is provided toreturn treated blood, saline, untreated blood components, treated bloodcomponents, and other fluids back to the patient. Inlet tube 1106 isprovided for delivering untreated whole blood (and a predeterminedamount of an anticoagulant fluid) from the patient to cassette 1100 forrouting and treatment within photopheresis kit 1000. Outlet tube 1119 isspecifically provided for delivering an anticoagulant fluid to inlettube 1106. It is preferable that all tubing is disposable medical gradesterile tubing. Flexible plastic tubing is the most preferred.

[0102] Cassette 1100 has five pump tube loops 1120, 1121, 1122, 1123,and 1124 for driving blood fluids throughout cassette 1100 andphotopheresis kit 1000. More specifically, pump tube loop 1121 loadsinto whole blood pump 1301 and respectively drives whole blood in andout of cassette 1100 via inlet tube 1106 and outlet tube 1115, passingthrough filter 1500 along the way. Pump loop tube 1120 loads into returnpump 1302 and drives blood fluids through filter 1500 and back to thepatient via outlet tube 1114. Pump loop tube 1122 loads into red bloodcell pump 1305 and draws red blood cells from centrifuge bowl 10 anddrives them into cassette 1100 via inlet line 1108. Pump loop tube 1123loads into anticoagulant pump 1304 and drives an anticoagulant fluidinto cassette 1100 via inlet tube 1124 and out of cassette 1100 to viaoutlet tube 1119, which connects with inlet tube 1106. Pump loop tube1124 loads into recirculation pump 1303 and drives blood fluids, such asplasma, through treatment bag 50 and irradiation chamber700 fromcassette 1100.

[0103] Each of peristaltic pumps 1301-1305 are activated when necessaryto perform the photopheresis treatment therapy according to anembodiment of the method of the present invention which is describedbelow in relation to FIGS. 26-27. Peristaltic pumps 1301-1305 can beoperated one at a time or in any combination. The pumps 1301-1305 workin conjunction with compression actuators 1240-1247 to direct fluidsthrough desired pathways of photopheresis kit 1000. Apertures 1137 and1157 are strategically located on base 1131 along the internal tubularcircuitry to facilitate proper routing. Through the use of compressionactuators 1240-1247, the fluids can be directed along any pathway orcombination thereof.

[0104] 1. The Filter Assembly

[0105] Filter 1500, which is located within cassette 1100 as describedabove, is illustrated in detail in FIGS. 6-10. Referring first to FIGS.6 and 7, filter 1500 is illustrated fully assembled. Filter 1500comprises a filter housing 1501. Filter housing 1501 is preferablyconstructed of a transparent or translucent medical grade plastic.However, the invention is not so limited and filter housing 1501 can beconstructed of any material that will not contaminate blood or otherfluids that are flowing therethrough.

[0106] Filter housing 1501 has four fluid connection ports extrudingtherefrom, namely whole blood inlet port 1502, whole blood outlet port1503, treated fluid inlet port 1504, and treated fluid outlet port 1505.Ports 1502-1505 are standard medical tubing connection ports that allowmedical tubing to be fluidly connected thereto. Ports 1502-1505respectively contain openings 1506, 1507, 1508 and 1509. Openings 1506,1507, 1508 and 1509 extend through ports 1502, 1503, 1504 and 1505,forming fluid passageways into filter housing 1501 at the desiredlocations.

[0107] Ports 1502, 1503, 1504 and 1505 are also used to secure filter1500 within cassette 1100. In doing so, ports 1502, 1503, 1504 and 1505can engage U-shaped fasteners 1135 of cassette 1100 (FIG. 3). Filterhousing 1501 also has a protrusion 1510 extending the bottom surface ofhousing floor 1518. Protrusion 1510 fits into a guide hole of base 1131of cassette 1100 (FIG. 3).

[0108] Referring now to FIG. 8, filter 1500 is illustrated in anexploded state. Filter housing 1501 is a two-piece assembly comprisingroof 1511 and base 1512. Roof 1511 is connected to base 1512 by anymeans known in the art, such as ultrasonic welding, heat welding,applying an adhesive, or by designing roof 1511 and base 1512 so that atight fit results between the two. While filter housing 1501 isillustrated as a two-piece assembly, filter housing 1501 can be either asingle piece structure or a multi-piece assembly.

[0109] Base 1512 has chamber separation wall 1513 extending upward froma top surface of housing floor 1518 (FIG. 7). When base 1512 and roof1511 are assembled, top surface 1515 of chamber separation wall 1513contacts the bottom surface of roof 1511, forming two chambers withinthe filter housing, whole blood chamber 1516 and filter chamber 1517.Fluid can not directly pass between whole blood chamber 1516 and filterchamber 1517.

[0110] Whole blood chamber 1516 is a substantially L-shaped chamberhaving floor 1514. Whole blood chamber 1516 has a whole blood inlet hole1519 and a whole blood outlet hole (not illustrated) in floor 1514.Whole blood inlet hole 1519 and the whole blood outlet hole are locatedat or near the ends of the substantially L-shaped whole blood chamber1516. Whole blood inlet hole 1519 forms a passageway with opening 1506of inlet port 1502 so that a fluid can flow into whole blood chamber1516. Similarly, the whole blood outlet hole (not illustrated) forms apassageway with opening 1507 of outlet port 1503 so that fluid can flowout of whole blood chamber 1516.

[0111] Filter chamber 1517 has floor 1520. Floor 1520 has elevated ridge1521 extending upward therefrom. Elevated ridge 1521 is rectangular andforms a perimeter. While elevated ridge 1521 is rectangular in theillustrated embodiment, elevated ridge 1521 can be any shape so long asit forms an enclosed perimeter. The height of elevated ridge 1521 isless than the height of chamber separation wall 1513. As such, when roof1511 and base 1512 are assembled, space exists between the top ofelevated ridge 1521 and the bottom surface of roof 1511. Elevated ridge1521 and chamber separation wall 1513 form a trench 1524 there between.

[0112] In order to facilitate fluid flow through filter chamber 1517,floor 1520 of filter chamber 1517 has treated fluid inlet hole 1522 andtreated fluid outlet hole 1523. Treated fluid inlet hole 1522 is locatedexterior of the perimeter formed by elevated ridge 1521 and forms apassageway with opening 1508 of inlet port 1504 so that a fluid can flowinto filter chamber 1517 from outside filter housing 1501. Treated fluidoutlet hole 1523 is located interior of the perimeter formed by elevatedridge 1521 and forms a passageway with opening 1509 of outlet port 1505so that a fluid can flow out of filter chamber 1517.

[0113] Filter 1500 further comprises filter element 1530. Filter element1530 comprises frame 1531 having filter media 1532 positioned therein.Frame 1531 has a neck 1534 that forms a filter inlet hole 1533. Filterelement 1530 is positioned in filter chamber 1517 so that frame 1531fits into trench 1524 and neck 1534 surrounds treated blood inlet hole1522. Filter inlet hole 1533 is aligned with treated fluid inlet hole1522 so that incoming fluid can freely flow through holes 1522 and 1533into filter chamber 1517. Frame 1531 of filter element 1530 forms ahermetic fit with elevated ridge 1521. All fluid that enters filterchamber 1517 through holes 1522 and 1533 must pass through filter media1532 in order to exit filter chamber 1517 via treated fluid outlet hole1523. Filter media 1532 preferably has a pore size of approximately 200microns. Filter media 1532 can be formed of woven mesh, such as wovenpolyester.

[0114] Filter chamber 1517 further comprises filter vent chamber 1540within roof 1511. Filter vent chamber 1540 has gas vent 1541 in the formof a hole (FIG. 9). Because gas vent 1541 opens into filter vent chamber1540 which in turn opens into filter chamber 1517, gases that build-upwithin filter chamber 1517 can escape through gas vent 1541. Similarly,whole blood chamber 1516 comprises blood vent chamber 1542 within roof1511. Blood vent chamber 1541 has gas vent 1543 in the form of a hole.Because gas vent 1543 opens into blood vent chamber 1542 which in turnopens into whole blood chamber 1517, gases that build-up in whole bloodchamber 1516 can escape via gas vent 1543.

[0115]FIG. 10 is a top view of filter 1500 having pressure sensors 1550and 1551 connected to gas vents 1541 and 1543. Pressure sensors 1550 and1551 are preferably pressure transducers. Pressure sensor 1550 isconnected to gas vent 1541 via vent tubing 1552. Vent tubing 1552 fitsinto gas vent 1541 so as to form a tight fit and seal. Because gas vent1541 opens into filter vent chamber 1540 which in turn opens into filterchamber 1517, the pressure in vent tubing 1552 is the same as in filterchamber 1517. By measuring the pressure in vent tubing 1552, pressuresensor 1550 also measures the pressure within filter chamber 1517.Similarly, pressure sensor 1551 is connected to gas vent 1543 via venttubing 1553. Vent tubing 1553 fits into gas vent 1543 so as to form atight fit and seal and pressure sensor 1551 measures the pressure withinwhole blood chamber 1516. Filter vent chamber 1540 and blood ventchamber 1542 extend through openings 1132 and 1133 of cassette 1100 whenfilter 1500 is positioned therein (FIG. 2). This allows the pressurewithin chambers 1516 and 1517 to be monitored while still protectingfilter chamber 1500 and the fluid connections thereto.

[0116] Pressure sensors 1550 and 1551 are coupled to controller 1554,which is a properly programmed processor. Controller 1554 can be a mainprocessor used to drive the entire system or can be a separate processorcoupled to a main processor. Pressure sensors 1550 and 1551 produceelectrical output signals representative of the pressure readings withinchambers 1517 and 1516 respectively. Controller 1554 receives on afrequent or continuous basis data representing the pressure withinchambers 1516 and 1517. Controller 1554 is programmed with valuesrepresenting desired pressures within chambers 1516 and 1517. Controller1554 continuously analyzes the pressure data it receives from pressuresensors 1550 and 1551 to determine whether the pressure readings arewithin a predetermined range from the desired pressure for chambers 1517and 1516. Controller 1554 is also coupled to whole blood pump 1301 andreturn pump 1302. In response to the pressure data received frompressure sensors 1551 and 1550, controller 1554 is programmed to controlthe speed of whole blood pump 1301 and return pump 1302, therebyadjusting the flow rates through the pumps 1301 and 1301. Adjustingthese flow rates in turn adjust the pressure within whole blood chambers1516 and filter chamber 1517 respectively. It is in this way that thepressure within the lines drawing and returning blood to and from thepatient is maintained at acceptable levels.

[0117] The functioning of filter 1500 during a photopheresis therapysession will now be discussed in relation to FIGS. 1, 6, and 10. Whilethe functioning of filter 1500 will be described in detail with respectto drawing whole blood from a patient and returning a component of saidwhole blood back into the patient after it is treated, the invention isnot so limited. Filter 1500 can be used in connection with almost anyfluid, including red blood cells, white blood cells, buffy coat, plasma,or a combination thereof.

[0118] Whole blood pump 1601 draws whole blood from a patient who isconnected to photopheresis kit 1000 via a needle connected to port 1193.The rotational speed of whole blood pump is set so that the pressure ofthe line drawing the whole blood from the patient is at an acceptablelevel. Upon being drawn from the patient, the whole blood passes intocassette 1100 via inlet tube 1106. Inlet tube 1106 is fluidly connectedto inlet port 1502 of filter 1500. The whole blood passes throughopening 1506 of inlet port 1502 and into L-shaped whole blood chamber1516. The whole blood enters chamber 1516 through inlet hole 1519 whichis located on floor 1514. As more whole blood enters chamber 1516, thewhole blood spills along floor 1514 until it reaches the whole bloodoutlet hole (not illustrated) at the other end of L-shaped whole bloodchamber 1516. As discussed above, the whole blood outlet whole forms apassageway with opening 1507 of outlet port 1503. The whole blood thatis within chamber 1516 flows across floor 1514, through the whole bloodoutlet hole, into outlet port 1503, and out of filter 1500 throughopening 1507.

[0119] As the whole blood passes through whole blood chamber 1516, gasesthat are trapped in the whole blood escape. These gases collect in bloodvent chamber 1542 and then escape via gas vent 1543. Pressure sensor1551 continuously monitors the pressure within blood chamber 1516through vent tube 1553 and transmits corresponding pressure data tocontroller 1554. Controller 1554 analyzes the received pressure data andif necessary adjusts the speed of whole blood pump 1301, therebyadjusting the flow rate and pressure within chamber 1516 and inlet tube1106. Controller 1554 adjust the pump speed to ensure that the pressureis within the desired pressure range.

[0120] The whole blood then exits filter 1500 through outlet port 1503and passes out of cassette 1100 via outlet tube 1115. The whole blood isthen separated into components and/or treated as described in detailbelow. Before being returned to the patient, this treated fluid (i.e.treated blood or blood components) must be filtered. Untreated fluidssuch as red blood cells also must be filtered and will subjected to thebelow filtering process. The treated fluid is fed into filter chamber1517 through opening 1508 of inlet port 1504. Inlet port 1504 is fluidlyconnected to pump loop tube 1120. The treated fluid enters filterchamber 1517 through inlet hole 1522 and passes through filter inlethole 1533 of filter element 1530. The treated fluid fills filter chamber1517 until it spills over frame 1531 of filter element 1530, which issecured to elevated ridge 1521. The treated fluid passes through filtermedia 1532. Filter media 1532 removes contaminants and other undesiredmaterials from the treated fluid while at the same facilitating therelease of trapped gases from the treated fluid. The treated fluid thatpasses through filter media 1532 gathers on floor 1520 of filter chamber1517 within the perimeter formed by elevated ridge 1521. This treatedfluid then passes into treated fluid outlet hole 1523 and out of filter1500 through opening 1506 of outlet port 1502. The treated fluid is thenreturned to the patient via outlet tube 1114, which is fluidly connectedto outlet port 1502. The treated fluid is driven through filter chamber1517 and outlet tube 1114 by return pump 1302.

[0121] Gases that are trapped in the treated fluid escape and collect infilter vent chamber 1540 as the treated fluid flows through filterchamber 1517. These gases then escape filter 1500 via gas vent 1541.Pressure sensor 1550 continuously monitors the pressure within filterchamber 1517 through vent tube 1552 and transmits corresponding pressuredata to controller 1554. Controller 1554 analyzes the received pressuredata and compares it to the desired pressure value and range. Ifnecessary, controller 1554 adjusts the speed of return pump 1302,thereby adjusting the flow rate and pressure within chamber 1517 andoutlet tube 1114.

[0122] B. Irradiation Chamber

[0123] FIGS. 11-16 illustrate irradiation chamber700 of photopheresiskit 1000 in detail. Referring first to FIG. 11, irradiation chamber700is formed by joining two plates, a front and a back plate having athickness of preferably about 0.06 in. to about 0.2 in., which arepreferably comprised of a material ideally transparent to the wavelengthof electromagnetic radiation. In the case of ultraviolet A radiation,polycarbonate has been found most preferred although other materialssuch as acrylic may be employed. Similarly, many known methods ofbonding may be employed and need not be expanded on here.

[0124] The first plate 702 has a first surface 712 and a second surface714. In a preferred embodiment the first plate 702 has a first port 705on a first surface 712, in fluid communications with the second surface714. The second surface 714 of the first plate 702 has a raised boundary726A defining an enclosure. The boundary 726A preferably extendssubstantially perpendicular from the second surface 714 (i.e. about80-100 degrees). Extending from the second surface 714 (preferablysubstantially perpendicularly) are raised partitions 720A. The boundary726A surrounds the partitions 720A. One end of each partition 720Aextends and contacts the boundary 726A.

[0125] The second plate 701 has a first surface 711 and a second surface713. In a preferred embodiment the second plate 701 preferably has asecond port 730 on a first surface 711, in fluid communications with thesecond surface 713. The second surface 713 of the back plate 701 has araised boundary 726B defining an enclosure. The boundary 726B preferablyextends substantially perpendicular from the second surface 713 (i.e.about 80-100 degrees). Extending from the second surface 713 (preferablysubstantially perpendicular) are raised partitions (720B). The boundary726B surrounds the partitions 720B. One end of each partition 720Aextends and contacts one side of boundary (726B).

[0126] The joining of the second surfaces of the first and second platesresults in a fluid tight junction between boundaries 726A and 726Bthereby forming boundary 726. Partitions 720A and 720B are also joinedforming a fluid tight junction thereby forming partition 720. Theboundary 726 forms an irradiation chamber700 and together with thepartitions 720 provides a pathway 710 having channels 715 for conductingfluid. The pathway maybe serpentine, zig-zag, or dove-tailed. Currentlypreferred is a serpentine pathway.

[0127] With reference to FIGS. 11 and 12, irradiation chamber700comprises a serpentine pathway 710 for conducting patient fluid, such asbuffy coat or white blood cells, from inlet port 705 to outlet port 730,i.e., the serpentine pathway 710 is in fluid communication with inletport 705 of front plate 702 and outlet port 730 of back plate 701.Patient fluid is supplied from cassette 1100 to inlet port 705 viaoutlet tube 1117. After photoactivation and passing through serpentinepathway 710, the treated patient fluid is returned to cassette 1100 viainlet tube 1112 (FIGS. 1 and 4). The patient fluid is driven byrecirculation pump 1303. Self-shielding effects of the cells is reducedwhile the cells are photoactivated by irradiation impinging upon bothsides of irradiation chamber700.

[0128]FIG. 11 shows pin 740 and recess 735 which align the two plates ofirradiation chamber prior to being joined together in a sealingarrangement by RF welding, heat impulse welding, solvent welding oradhesive bonding. Joining of the plates by adhesive bonding and RFwelding is more preferred. Joining of the front and back plates by RFwelding is most preferred as the design of the raised partitions 720 andperimeter 725 minimizes flashing and allows for even application of RFenergy. Locations of pin 740 and recess 735 may be inside serpentinepathway 710 or outside of serpentine pathway 710. FIG. 2 also shows aview of an irradiation chamber with axis L. Rotation of chamber 700 180degree about axis L gives the original configuration of the irradiationchamber. The irradiation chamber of the present invention has C₂symmetry about axis L.

[0129] Referring to FIGS. 11, 13, and 16, the leukocyte enriched blood,plasma, and priming solution are delivered through inlet port 705 offront plate 702 of irradiation chamber700 into channel 715. The channel715 in the irradiation chamber700 is relatively “thin” (e.g. on theorder of approximately 0.04″ as distance between two plates) in order topresent large surface area of leukocyte rich blood to irradiation andreduce the self-shielding effects encountered with lower surfacearea/volume ratios. The cross section shape of channel 715 issubstantially rectangular (e.g. rectangular, rhomboidal or trapezoidal)which has as its long side the distance between partition 720 and thedistance between the plates as its short side. The shape of the crosssection is designed for optimal irradiation of cells passing throughchannel 715. While a serpentine pathway 710 is preferred in order toavoid or minimize stagnant areas of flow, other arrangements arecontemplated.

[0130] The irradiation chamber 700 allows efficient activation ofphotoactivatable agents by irradiation from a light array assembly, suchas the PHOTOSETTE®'s two banks of UVA lamps (758) for activation (FIG.16). The irradiation plate and UVA light assembly (759) are designed tobe used in a setting where edge 706 is oriented downward and edge 707points upward. In this orientation, fluids entering input port 705 canexit from outlet port 730 with the aid of gravity. In the most preferredembodiment, irradiation of both sides of the irradiation chamber takesplace concurrently while still permitting facile removal of the chamber.UVA light assembly 759 is located within UV chamber 750 of permanenttower system 2000 (FIGS. 17 and 18).

[0131] The irradiation chamber's fluid pathway loops to form two or morechannels in which the leukocyte-enriched blood is circulated duringphotoactivation by UVA light. Preferably, irradiation chamber 700 hasbetween 4 to 12 channels. More preferably, the irradiation chamber has 6to 8 channels. Most preferably, the irradiation chamber has 8 channels.

[0132]FIG. 14 shows cut-away views of the irradiation chamber. Thechannels 715 of serpentine pathway 710 are formed by the joining ofraised partition 720 and perimeter 726 of the plates.

[0133] The irradiation chamber of the present invention can be made froma biocompatible material and can be sterilized by known methods such asheating, radiation exposure or treatment with ethylene oxide (ETO).

[0134] The method of irradiating cells using irradiation chamber 700during extracorporeal treatment of cells with electromagnetic radiation(UVA) to be used in the treatment of a patient (such as to induceapoptosis in the cells and administer the cells into the patient) willnow be discussed. Preferably the cells treated will be white cells.

[0135] In one embodiment of this method, a photoactivatable orphotosensitive compound is first administered to at least a portion ofthe blood of a recipient prior to the extracorporeal treatment of thecells. The photoactivatable or photosensitive compound may beadministered in vivo (e.g., orally or intravenously). The photosensitivecompound, when administered in vivo may be administered orally, but alsomay be administered intravenously and/or by other conventionaladministration routes. The oral dosage of the photosensitive compoundmay be in the range of about 0.3 to about 0.7 mg/kg., more specifically,about 0.6 mg/kg.

[0136] When administered orally, the photosensitive compound may beadministered at least about one hour prior to the photopheresistreatment and no more than about three hours prior to the photopheresistreatment. If administered intravenously, the times would be shorter.Alternatively, the photosensitive compound may be administered prior toor contemporaneously with exposure to ultraviolet light. Thephotosensitive compound may be administered to whole blood or a fractionthereof provided that the target blood cells or blood components receivethe photosensitive compound. A portion of the blood could first beprocessed using known methods to substantially remove the erythrocytesand the photoactive compound may then be administered to the resultingenriched leukocyte fraction. In one embodiment, the blood cells comprisewhite blood cells, specifically, T-cells.

[0137] The photoactivatable or photosensitive compound may, in the caseof some psoralens, be capable of binding to nucleic acids uponactivation by exposure to electromagnetic radiation of a prescribedspectrum, e.g., ultraviolet light.

[0138] Photoactive compounds may include, but are not limited to,compounds known as psoralens (or furocoumarins) as well as psoralenderivatives such as those described in, for example, U.S. Pat. No.4,321,919 and U.S. Pat. No. 5,399,719. The photoactivatable orphotosensitive compounds that may be used in accordance with the presentinvention include, but are not limited to, psoralen and psoralenderivatives; 8-methoxypsoralen; 4,5′8-trimethylpsoralen;5-methoxypsoralen; 4-methylpsoralen; 4,4-dimethylpsoralen;4-5′-dimethylpsoralen; 4′-aminomethyl-4,5′,8-trimethylpsoralen;4′-hydroxymethyl-4,5′,8-trimethylpsoralen; 4′,8-methoxypsoralen; and a4′-(omega-amino-2-oxa) alkyl-4,5′,8-trimethylpsoralen, including but notlimited to 4′-(4-amino-2-oxa)butyl-4,5′,8-trimethylpsoralen. In oneembodiment, the photosensitive compound that may be used comprises thepsoralen derivative, amotosalen (S-59) (Cerus, Corp., Concord, Calif.).See, e.g., U.S. Pat. Nos. 6,552,286; 6,469,052; and 6,420,570. Inanother embodiment, the photosensitive compound that may be used inaccordance with the invention comprises 8-methoxypsoralen.

[0139] Methoxsalen is a naturally occurring photoactive substance foundin the seed of the Ammi majus (umbelliferae plant). It belongs to aclass of compounds known as psoralens or furocoumarins. The chemicalname is 9-methoxy-7H-furo[3,2-g][1]-benzopyran-7-one. The formulation ofthe drug is a sterile liquid at a concentration of 20 mcg/mL in a 10 mLvial. See http://www.therakos.com/TherakosUS/pdf/uvadexpi.pdf.Toxicology studies of extracorporeal photopheresis and different dosagesof UVADEX® and ultraviolet light in beagle dogs is located in theinvestigator's brochure.

[0140] Next, the portion of the subject's blood, recipient's blood, orthe donor's blood to which the photoactive compound has beenadministered is treated by subjecting the portion of the blood tophotopheresis using ultraviolet light. The photopheresis treatment maybe carried out using long wavelength ultraviolet light (UVA) at awavelength within the range of 320 to 400 nm. Such a range is notlimiting, however, but is merely provided as an example. The exposure toultraviolet light during the photopheresis treatment may have a durationof sufficient length to deliver, for example, about 1-2 J/cm² to theblood.

[0141] The photopheresis step is carried out in vitro by installingirradiation chamber 700 into photoactivation chamber 750 of permanenttower system 2000 (FIGS. 17 and 18). In one embodiment, when thephotopheresis step is carried out in vitro, at least a fraction of thetreated blood is returned to the subject, recipient, or donor. Thetreated blood or the treated enriched leukocyte fraction (as the casemay be) may then be administered back to the subject, recipient, ordonor.

[0142] The photopheresis process consists of three phases including: 1)the collection of a buffy-coat fraction (leukocyte-enriched), 2)irradiation of the collected buffy coat fraction, and 3) reinfusion ofthe treated white blood cells. This process will be discussed below ingreater detail. Generally, whole blood is centrifuged and separated incentrifuge bowl 10. A total of approximately 240 ml of buffy coat and300 ml of plasma are separated and saved for UVA irradiation.

[0143] The collected plasma and buffy coat are mixed with heparinizednormal saline and UVADEX®. (water soluble 8-methoxypsoralin). Thismixture flows in a 1.4 mm thick layer through the irradiation chamber ofthe present invention. The irradiation chamber 700, is inserted inphotoactivation chamber 750 of tower system 2000 between two banks ofUVA lamps of the PHOTOSETTE® (FIG. 15). PHOTOSETTE® UVA lamps irradiateboth sides of this UVA-transparent irradiation chamber 700, permittingexposure to ultraviolet A light, yielding an average exposure perlymphocyte of 1-2 J/cm². Following the photoactivation period, the cellsare removed from the irradiation chamber 700.

[0144] In a preferred embodiment of the present invention the cells areremoved by the action of gravity and any cells remaining in the chamberare displaced from the chamber with additional fluid selected from thegroup consisting of saline, plasma, and combinations thereof. Forpatients who are small such as children (e.g. under 30 kg) or patientswhose vascular system is easily overloaded with fluids the amount ofadditional fluid used to was the irradiation chamber will preferably benot more than 2× the volume of the chamber, preferably not more than 1×the volume of the chamber, more preferably not more than 0.5× the volumeof the chamber 0.25× the volume of the chamber. The treated cells volumeis reinfused to the patient.

[0145] For a description of similar photopheresis systems and methods,see U.S. patent application Ser. No. 09/480,893, which is expresslyincorporated herein by reference. Also useful herein are the methods andsystems described in U.S. Pat. Nos. 5,951,509; 5,985,914; 5,984,887,4,464,166; 4,428,744; 4,398,906; 4,321,919; PCT Publication Nos. WO97/36634; and WO 97/36581, all of which are entirely expresslyincorporated herein by reference.

[0146] The effective amount of light energy that is delivered to thebiological fluids may be determined using the methods and systemsdescribed in U.S. Pat. No. 6,219,584, which is entirely expresslyincorporated herein by reference. Indeed, the application of ECP to thevarious diseases described herein may require an adjustment of theamount of light energy to optimize the treatment process.

[0147] Furthermore, the photosensitizing agent used in the ECP processmay be removed prior to returning the treated biological fluid to thepatient. For example, Methoxsalen (UVADEX®) is utilized in the ECPprocess. Methoxsalen belong to a group of compounds known as psoralens.The exposure to methoxsalen or other psoralens may cause undesirableeffects on the subject, recipient, or donor such as phototoxicity orother toxic effects associated with psoralen and their decompositionproducts. Therefore, the psoralen, psoralen derivatives, or psoralendecomposition products that may remain in the biological fluid may beremoved after UV exposure. A process for the removal of psoralenbiological fluids is described in U.S. Pat. No. 6,228,995, which isentirely expressly incorporated herein by reference.

[0148] C. Centrifuge Bowl

[0149] In a specific embodiment, the present invention relates tomethods and apparatus that separate fluid components, such as, forexample, the components of a biological fluid by density or weight.Biological fluids encompass fluids that comprise, exist in, or are usedin, or delivered to living organisms. Indeed, biological fluids maycomprise bodily fluids and their components, such as blood cells,plasma, and other fluids that comprise biological components, includingliving organisms such as bacteria, cells, or other cellular components.Biological fluids may also comprise whole blood or specific whole bloodcomponents, including red blood cells, platelets, white blood cells, andprecursor cells. In particular, it may be desirable to remove blood froma patient for treatment, such as for example, extracorporeal treatment.It is to be understood, however, that the present invention is adaptableto use with various centrifugal processing apparatus, and the specificexample given herein is merely for illustrative purposes. Other uses forthe separation techniques and apparatus may include other medicalprocesses such as dialysis, chemotherapy, platelet separation andremoval, and separation and removal of other specific cells.Additionally, the present invention may be used to separate other typesof fluids that include a wide variety of non-medical uses, such as, forexample, oil and fluid component separation. All components used in thepresent invention should not adversely affect biological fluids orrender them unsuitable for their intended uses, such as those describedherein and may be made of any suitable material compatible with usesdescribed herein including, but not limited to plastics, such aspolycarbonate, methyl methacrylate, styrene-acrylonitrile, acrylic,styrene, acrylonitrile or any other plastic. Where parts of the presentinvention are indicated to be attached together and form a fluid tightseal any appropriate conventional means of joining the parts may be usedincluding but not limited to, adhesives, ultrasonic welding or RFwelding.

[0150] The present invention has several advantages over centrifugeswhat use conventional Latham bowl. The Latham bowl in the UVAR® XTS™system has one inlet port that allows whole blood to come into the bowland one outlet port that allows plasma and buffy coat to come out.Having only two ports limits the volume of buffy coat that can becollected per cycle. Each cycle involves filling the bowl with wholeblood; 2) spinning the bowl to separate whole blood into plasma, buffycoat, and red blood cells; 3) collecting buffy coat for treatment, 4)bringing the bowl to rest; and 5) returning collected plasma and redblood cells. This buffy coat collection method may be characterized asbeing “batch-like” as the volume of buffy coat required for irradiationtreatment can only be collected after several cycles of buffy coatcollection. The limited volume of collected buffy coat per cycle resultsfrom the accumulated red blood cells remained inside the bowl. Thus theaccumulated red blood cells that can only be emptied at the end of abuffy coat collection cycle is an inherent limitation of the LathamBowl.

[0151] The bowl of the instant invention has three separate fluidconduits that can be used as an inlet port and two outlet ports. Theadditional fluid conduits allows for 1) reduce patient treatment time byhaving continuous spinning during the entire buffy coat collectionprocess without having to stop spinning the bowl for removal ofaccumulated red blood cells; 2) treat small blood volume patients; byhaving collected red blood cells returned to patients continuously,these patients may be more amenable to medical treatments requiring theuse of the buffy coat or fractions thereof such as extracorporealphotopheresis; 3) better separation of different components of fractionsof cells within the buffy coat due to the increased spinning or rotationtime and 4) the ability to separate high density red blood cellsfractions from whole blood. This centrifuge bowl also provides theopportunity for reduced treatment time for any medical procedurerequiring buffy coat fractions to be collected from patients that aresubstantially free of red blood cells, such as extra corporealphotopheresis.

[0152] To achieve the objects in accordance with the purpose of thepresent invention, as embodied and broadly described herein, FIGS. 35and 36 depict specific embodiments of the present invention. Theembodiment depicted in FIG. 35 comprises a centrifuge bowl 10A, conduitassembly 860A, frame 910A and stationary restraint 918A. The centrifugebowl 10A is in fluid communications with external conduit 20A of conduitassembly 860A. Lower sleeve end 832A (FIG. 46) of connection sleeve 500Ais secured to bowl 10A. Upper sleeve end 831A of connection sleeve 500Ais secured to external conduit 20A, connecting the external conduit 20Ato bowl 10A and providing fluid communications from external conduit 20Ato bowl 10A. The fluid communications enables fluid 800 to be suppliedthrough external conduit 20A to the bowl 10A. Similarly this fluidcommunications also enables separated fluid components 810 and 820 to beremoved from bowl 10A through external conduit 20A. Bowl 10A and frame910A are adapted to be rotated around center axis 11A.

[0153] Referring to FIG. 36, bowl 10A comprises outer housing 100A,connection sleeve 500A, top core 200A, bottom core 201A, and housingfloor 180A. Outer housing 100A may be constructed of any suitablebiocompatible material as previously described for the purpose of theillustration in FIG. 36 the outer housing 100A is constructed of clearplastic so that cores 200A and 201A are visible there through. Outerhousing 100A is attached to a housing floor 180A, which in turncomprises protrusions 150A for locking bowl 10A into a rotational devicesuch as rotational device 900A. Bowl 10A is preferably simplified inconstruction and is easy to manufacture by molding or other knownmanufacturing processes, such that it may be disposable or used for alimited number of treatments, and is most preferably capable ofcontaining about 125 ml of fluid, such fluid possibly being pressurized.In alternative embodiments, the volume capacity of the bowl may varydepending upon the health of the patient and his or her allowableextracorporeal volume. The volume capacity of the bowl may also varydepending upon the use of the bowl or the particular treatment for whichthe bowl is utilized. Additionally, to avoid contamination of biologicalfluids, or exposure of persons involved in the processing operation tothe fluids, the transfer operations are preferably carried out within asealed flow system, possibly pressurized, preferably formed of flexibleplastic or similar material which can be disposed of after each use.

[0154] As is illustrated in FIGS. 36 and 37, the outer housing 100A issubstantially conical having an upper housing end 110A, an outer housingwall 120A and a lower housing end 190A. Outer housing 100A may be madeof plastic (such as those plastics listed previously), or any othersuitable material. Upper housing end 110A has an outer surface 110B,inner surface 110C and housing outlet 700A providing a passage betweensaid surfaces. Preferably the upper housing will also have a neck 115Aformed about the housing outlet 700A. The housing outlet 700A and neck115A are sized to allow body 830A of the connection sleeve 500A to passthrough while retaining sleeve flange 790A, which extends from the body830A of connection sleeve 500A. In one embodiment of the presentinvention an o-ring 791A may be inserted between the sleeve flange 790Aand inner surface 110C of the housing end 110A to ensure a fluid tightseal is provided. In an alternative embodiment of the present inventionillustrated in FIG. 53, a second sleeve flange 790B extends from thebody 830A of connection sleeve 500B distal to the sleeve flange 790A.Both sleeve flange 790A and 790B being adapted to fit within neck 115Aand retain o-ring 791A therebetween. A fluid tight seal is provided inthis embodiment by the o-ring contacting body 830A and inner surface110C of the housing end 110A adjacent to the neck 115A. However,connection sleeve 500A can be secured to bowl 10A by any suitable means,including for example, a lip, groove, or tight fit and adhesive with acomponent of bowl 10A. The outer housing wall joins the upper housingend 110A and lower housing end 190A. Lower housing end 190A is attachedto a housing floor 180A of greater diameter than upper end 110A. Housingfloor 180A is adapted to mate with the lower housing end 190A andprovide a fluid tight seal therewith. Any conventional means may be usedto secure the lower housing end 190A to the housing floor 180A,including but not limited to, adhesives, ultrasonic welding or RFwelding. Housing floor 180A may have an indentation 185A that is used tocollect denser fluid 810. The diameter of outer housing 100A increasesfrom upper housing end 110A to lower housing end 190A.

[0155] Outer housing 100A is adapted to rotatably connect to arotational device 900 (FIG. 35), such as for example, a rotor drivesystem or a rotating bracket 910. The rotatable connection may, forexample, be a bearing that allows free rotation of bowl 10A. Outerhousing 100A preferably has a locking mechanism. The locking mechanismmay be one or more protrusions 150A designed to interact withcorresponding indentations in a centrifuge container or any othersuitable interconnect or locking mechanism or equivalent known in theart. The locking mechanism may also comprise a key slot 160 (FIG. 51).

[0156] Referring to FIG. 37, outer housing 100A and the base 180A definean interior volume 710A in which cores 200A and 201A will fit when bowl10A is assembled. When fully assembled, cores 200A and 201A are fullywithin interior volume 710A of outer housing 100A, occupying a coaxialvolume of interior volume 710A about axis 11A.

[0157] Referring to FIGS. 38, 40 and 44, the top core 200A and bottomcore 201A are substantially conical and respectively have upper coreends 205A, 206A; outer core walls 210A, 211A; and lower core ends 295A,296A. The cores 200A, 201A occupy coaxial volumes of interior volume710A of bowl 10A and forming separation volume 220A between upper end205A and outer wall 210A of top core 200A and outer wall 211A and lowercore end 296A of bottom core 201A and outer housing 100A. Separationvolume 220A is that space of interior volume 710A that is between cores200A and 201A and outer housing 100A.

[0158] As depicted in FIGS. 40 and 41 top core 200A comprises upper coreend 205A and a lower core end 295A that are joined by outer core wall210A. The outer core wall 210A having an outer surface 210B and innerwall surface 210C and a lower edge 210D. The diameter of top core 200Apreferably increases from upper core end 205A to lower core end 295A.Upper core end 205A also comprises an outer surface 205B and an innersurface 205C. Centrally located about center axis and extendingperpendicularly from the upper surface 205B is lumen connector 481A.Lumen connector 481A has a top surface 482A and a wall surface 482B. Topsurface 482A has two passages 303B and 325D that provide fluidcommunications through the upper core end 205A with second bowl channel410A and first bowl channel 420A respectively. Second bowl channel 410Ais a conduit that has a conduit wall 325A that extends perpendicularlyfrom the inner surface 481C of lumen connector 481A.

[0159] As shown on FIGS. 39B, 39A and 40, second bowl channel 410 hasfluid communication with conduit channel 760A through conduit 321Ahaving a first end 321B and a second end 321C that is adapted to fitinto passage 325D of lumen connector 481A. In operation conduit channel760A of external conduit 20A has fluid communication with bowl channel410A. First bowl channel 420A is a second conduit that has a channelwall 401A that extends substantially perpendicularly from inner surface481C of the lumen connector 481A. As shown in FIGS. 39A, 39B and 40,first bowl channel 420A has fluid communication with conduit channel780A of external conduit 20A through hollow cylinder 322A having a firstend 322B and a second end 322C adapted to fit opening 303B top surface482A. As is illustrated in one embodiment of the present invention,second bowl channel 410A is disposed within first bowl channel 420A. Inan alternative embodiment of the present invention illustrated in FIG.53, conduit wall 325A may be composed of upper part 325F and lower part325G and be fused with channel walls 401A and 402A.

[0160] Top surface 482A also has indentation 483A which provides fluidcommunications with chamber 740A. When assembled, chamber 740A isdefined by lumen mounting recess 851A less the volumes occupied byhollow cylinders 321A and 322A in the connection junction of connectionsleeve 500A and lumen connector 481A. Chamber 740A has fluidcommunication with conduit channel 770A and with separation volume 220Anear neck 115A through indentation 483A. Thus indentation 483A forms apassageway for the removal of second separated fluid component 820through bowl chamber 740A. Optionally present on the outer surface 205Bare a plurality of spacers 207A which extend from the outer surface andcontact the inner surface 110C of the upper housing end 110A to ensurefluid communications between the separation volume 220A and thepassageway formed by the indentations 483A.

[0161] In an alternative embodiment illustrated in FIGS. 53, 54 and 55,conduits 321A and 322A may be affixed to openings 325D and 303B in thetop surface 482A of the lumen connector 481 A. Additionally,indentations 483A may form a plurality channels in the lumen connector481A and be adapted to form chamber 740B when connected to connectionsleeve 500A or 500B. Chamber 740B is adapted to have one or moresurfaces 742A that can mate with the male end 853A of the connectionsleeve 500A (male end 853A surrounds end 861 of external conduit 20A).To facilitate the correct orientation of the connection sleeve 500A tothe lumen connector 481A the shape of the male end 853A and chamber 740Bmay be nonsymmetrical or as is illustrated in FIGS. 53, 54 and 55 aguide 855A may be provided which extends from the top surface of thelumen connector 481A and is adapted to fit within opening 857A of thesleeve flange 790A.

[0162] Referring back to FIG. 40, the lower core end 295A comprises anupper plate 299A having a top surface 298A, a bottom surface 297A, andan edge 299B that attaches and makes direct contact with lower edge 210Dof the outer core wall 210A. The edge 299B of the upper plate 299A isadapted to be joined with lower edge 210D of outer core wall 210A andform a fluid tight seal therewith. Extending perpendicularly from thetop surface 298A of upper plate 299A is a channel wall 402A, having anupper end 402B and a lower end 402C and surrounds opening 303A which issubstantially in the center of upper plate 299A. A number of fins 403A,attached to the outside surface of channel wall 402A and top surface298A, supports lumen wall 402A. The channel wall 402A is adapted to matewith channel wall 401A forming a fluid tight seal and providing lumen400A. First bowl channel 420A is in fluid communications with conduitchannel 780A of external conduit 20A through conduit 322A. Opening 303Aprovides fluid communications from lumen 400A to separation volume 220Aas will be further discussed. First bowl channel 420A also surroundssecond bowl channel 410A.

[0163] Referring to FIGS. 43A, 43B and 44, bottom core 201A comprises anupper core end 206A, a outer core wall 211A and a lower core end 296A.The outer core wall 211A having an outer surface 211B, an inner wall211C and lower edge 211D. The diameter of bottom core 201A preferablyincreases from upper core end 206A to lower core end 296A. Bottom core201A also has a top surface 309A and a bottom surface 309B. Top surface309A has an indentation 186A (preferably generally circular) substantialin the center of the surface 309A of the upper core end 206A. Theindentation 186A has an upper surface 186B and an inner surface 186C.The upper surface 186B of the indentation 186A has therein an opening324D which extends through to the inner surface 186C. In an alternativeembodiment of the present invention illustrated in FIG. 53, the uppersurface 186B, may also have a recess a186D adapted to receive an o-ringand form a fluid type seal around the lower end of 325B of conduit wall325A. Extending perpendicularly from inner surface 186C around saidopening 324D is conduit wall 324A having a distal end 324B. On the topsurface 309A extending from the indentation 186A to the outer surface211B of the outer core wall 211A are one or more channels 305A. The topsurface 309A may be horizontal or slope upward or downward fromindentation 186A. If top surface 309A slopes upward or downward fromindentation 186A to core end 206A, one skilled in the art would be ableto adjust the shapes of upper plate 299A and upper core end 295Aaccordingly. Channels 305A may have an even depth through out the lengthof the channel 305A. However, channel 305A may slope downward or upwardradially from the center. One skilled in the art would see that if topsurface 309A slopes upward or downward and channel 305A has a constantdepth, then channel 305A slopes upward or downward accordingly.

[0164] Referring to FIG. 38, the bottom surface 297A of upper plate 299Ais in direct contact with the top surface area 309A of bottom core 201Awhen completely assembled. This contact forms a fluid tight seal betweenthe two surface areas forming an opening 305B from the indentation 186Ato channel 305A. A second opening 305C from channel 305A is formed inthe outer surface 211B of outer core wall 211A. The opening 305Bprovides fluid communications from indentation 186A through channel 305Aand opening 305C to separation volume 220A (FIGS. 38 and 40). Thus fluid800 flows through conduit channel 780A and subsequently passes throughfirst bowl channel 420A. From first bowl channel 420A, fluid 800 thengoes to through channel 305A to the separation volume 220A.

[0165] Referring to FIGS. 43A and 44, the lower core end 296A has alower plate 300A, which has a top surface 300B, a bottom surface 300Cand outer edge 300D. Extending from the bottom surface 300C of the lowerplate 300 are one or more protrusions 301A. The outer edge 300D isadapted to be attached to the lower edge 211D of the outer core wall211A and provide a fluid tight seal therewith. Positioned above housingfloor 180A, lower plate 300A is circular and curves upward radially fromits center (illustrated in FIG. 44). Alternatively, lower plate 300A canbe flat. As shown in FIG. 38 when positioned above housing floor 180A, avolume 220C exists between lower plate 300A and housing floor 180A. Thisvolume 220C is in fluid communication with separation volume 220A. Lowerplate 300A may be made of plastic or any other suitable material.Additionally, extending substantially perpendicularly from the lowersurface 300C of lower plate 300A is a conduit 320A. Conduit 320A has afirst end 320B that extends into the space 220C between lower plate 300Aand housing floor 180A and a second end 320C that extends above the topsurface 300B of lower plate 300A. The diameter of conduit 320A isadapted to have a tight fit with conduit wall end 324B. The volumeinside conduit walls 324A and 325A comprises a lumen 400B. The volumedefined by lower plate 300A, inner surface 211C, and ceiling 253A ofbottom core 201A, excluding second bowl channel 410A, may comprise ofair or a solid material (See FIGS. 43B and 44).

[0166] In an alternative embodiment of the present invention asillustrated in FIG. 53, support walls 405A and 407A may be optionallypresent. Support wall 405A extends perpendicularly from bottom surface309B. Support wall 407A extends perpendicularly from the top surface300B of lower plate 300A and connects with support wall 405A when thebottom core 201A is assembled. Conduit wall 324A may be connected toconduit 320A to form a fluid tight seal and conduits 324A, 320A may befused respectively with supports walls 405A and 407A. Additionallypresent extending from the bottom surface 300C of lower plate 300A areone or more orientation spacers 409A that mate within indentation 185A.

[0167] As will be readily apparent to one of ordinary skill in the art,the bowl 10A will need to be balanced about center axis 11A.Accordingly, weights may be added as part of the device as isappropriate to facilitate the balancing of the bowl 10A such as weight408A illustrated in FIG. 53.

[0168] Referring to FIG. 38, bowl 10A is adapted so that outer housing100A, cores 200A and 201A, lower plate 300A and upper plate 299A,housing floor 180A, external conduits 20A and connection sleeve 500A,and lumens 400A and 400B are in connection and rotate together. Housingfloor 180A of outer housing 100A comprises recesses 181A on its topsurface and these recesses are shaped to fit protrusion 301A of lowerplate 300A. As shown, lower plate 300A has round protrusion 301A on itsbottom surface 300C to restrict movement of lower plate 300A withrespect to housing floor 180A. When assembled, each single protrusion301A on the bottom surface of lower plate 300A forms a tight fit withrecess 181A on housing floor 180A. Thus, when outer housing 100A isrotated, external conduit 20A and connection sleeve 500A, top core 200A,upper plate 299A, bottom core 201A, lower plate 300A, housing floor180A, and lumens 400A and 400B will rotate therewith.

[0169] As illustrated in FIG. 38 lumen 400A allows whole blood 800 tocome into bowl 10A via a first bowl channel 420A. First bowl channel420A provides a passageway for inflow of fluid 800 through lumen 400A toindention 186A and then to the separation volume 220A through channel305A. Lumen 400A is located inside top core 200A. Lumen 400A has aheight from upper lumen end 480A and lower lumen end 402C. Lumen 400A isformed by the connection of channel wall 401A extending from the innersurface 481C of lumen connector 481A and channel wall 402A extendingfrom the top surface 298A of upper plate 299A. Channel wall 401A issupported by a plurality of fins 251A which are attached to the innerwall surface 210C of the outer core wall 210A and inner surface 205C ofthe upper core end 205A, and channel wall 402A is supported by aplurality of fins 403A (FIG. 40). It can readily be seen that height oflumen 400A can be adjusted by changing the sizes and shapes of core200A, channel wall 401A, channel wall 402A, conduit wall 325A, and theheight of conduit wall 324A.

[0170] As illustrated in FIG. 38, lumen 400A, from upper lumen end 480Ato lower lumen end 402C, encloses an inner lumen 400B. Lower lumen end402C has an opening 303A which is in fluid communication with separationvolume 220A through a number of channel 305A. In the illustratedembodiment lumen 400A comprises first bowl channel 420A. Second bowlchannel 410A is located inside first bowl channel 420A of the top core200A and is enclosed therein from lumen end 480A and to lumen 402C.Furthermore, second bowl channel 410A forms a passageway through lumen400B from below lower plate 300A for the removal of a first separatedfluid component 810 that gathers in indentation 185A of housing floor180A. Second bowl channel 410A extends from housing floor 180A of outerhousing 100A through lumen 400B and to conduit channel 760A of externalconduit 20A.

[0171] Referring FIG. 38 (shown without conduit 321C), inner lumen 400Ballows red blood cells 810 to exit bowl 10A via a second bowl channel410A that provides fluid communication from the housing floor aboveindentation 185A to opening 324E. Inner lumen 400B has an upper conduitend 325C and a lower conduit end 324B and comprises two conduit walls324A and 325A which are connected in a fluid tight manner and formsecond bowl channel 410A that has a smaller diameter than and isseparate and distinct from first bowl channel 420A. Conduit wall 325A issupported by a fin 251A that extends through channel wall 401A andattaches to conduit wall 325A. Unlike lumen 400A which has one end nearindentation 186A, lumen 400B extends beyond indentation 186A and throughbottom plate 300A. The first conduit wall 325A has an upper end 325Cwhich has an opening 325D on the top surface 482A of lumen connector481A and a lower end 325B having an opening 325E adapted to fit tightlywith upper end 324C of conduit wall 324A. Upper end 324C of conduit wall324A is higher than indentation 186A and has an opening 324D. Conduitwall 324A also has end lower end 324B and is supported by a plurality offins 252A. Lower end 324B having opening 325E is adapted to connect toconduit 320A having opening 302A located near the center of lower plate300A. The connection of openings 325E and 302A provide fluidcommunication between lumen 400B and the space 220C between lower plate300A and housing floor 180A. The space 220C between lower plate 300A andhousing floor 180A in turn has fluid communication with separationvolume 220A.

[0172] Conduit 320A provides a tight fit with lower end 324B, providingsupport for second bowl channel 410A. Each bowl channel 420A and 410Amay be made of any type of flexible or rigid tubing (such as medicaltubing) or other such device providing a sealed passageway, possibly forpressurized or unpressurized fluid flow, and which preferably can bedisposable and sterilizable, i.e., of simple and efficient manufacture.

[0173] 1. Drive Tube

[0174] As illustrated in FIGS. 39A and 39B, conduit assembly 860A isattached to bowl 10A via connection sleeve 500A which is attached ontothe first end 861A of external conduit 20A having a first conduitchannel 780A, a second conduit channel 760A, and a third conduit channel770A. Each conduit channel has fluid communication with a first bowlchannel 420A, a second bowl channel 410A, and a bowl chamber 740A. Thethree conduit channels are equally spaced 120° apart and equal indiameter in external conduit 20A (See FIG. 50). When fluidly connect toexternal conduit 20A and bowl 10A, conduit channel 780A is fluidlyconnected with first bowl channel 420A for inflowing fluid 800 fromexternal conduit 20A into bowl 10A for separation. Similarly, secondconduit channel 760A fluidly connects to second bowl channel 410A forremoving first separated fluid component 810 from bowl 10A into externalconduit 20A. Finally, third conduit channel 770A connects to bowlchamber 740A for removing second separated fluid component 820 from bowl10A.

[0175] As is illustrated in FIG. 45, external conduit 20A has aconnection sleeve 500A on the first end 861A and an anchor sleeve 870Aon the second end 862A of external conduit 20A. Optionally presentbetween the connection sleeve 500A and the anchor sleeve 870A onexternal conduit 20A are a first shoulder 882 and a second shoulder 884which extend perpendicularly from the external conduit 20A and are of alarger diameter. Between the connection sleeve 500A and anchor sleeve870A (or if present the first and second shoulder 882, 884) are a firstand second bearing rings 871A and 872A. External conduit 20A, anchorsleeve 870A, and connection sleeve may be prepared from the same ordifferent biocompatible materials of suitable strength and flexibilityfor use in this type of tubing in a centrifuge (one such preferredmaterial is HYTREL®). The connection sleeve 500A and the anchor sleeve870A may be attached through any suitable means such as adhesives,welding etc., however, for ease of manufacture it is preferred that theconnection sleeve 500A and the anchor sleeve 870A be overmolded to theexternal conduit 20A.

[0176] Referring to FIGS. 45, 48 and 49 anchor sleeve 870A comprises abody 877B having a first anchor end 873A and second anchor end 874A.Anchor sleeve 870A is attached to second conduit end 862A of externalconduit 20A (preferably by overmolding) and increases in diameter fromfirst collar 873A to the collar 874A. Spaced distally from second end874A is a collar 886A, which extends perpendicularly from body 877B andof a larger diameter than the body 877B of the anchor sleeve 870A. Aplurality of ribs 877A having a first rib end 877B between the collar886A and second anchor end 873A and a second rib end 877C extendingbeyond the first anchor end 873A are attached to the body 877B. Thesecond rib ends 877C are joined together by a ring 880A, which is alsoattached to external conduit 20A. The ribs 877A run parallel to theexternal conduit 20A and are preferably placed over the region whereconduit channels 760A, 770A, and 780A, are closest to the surface of theexternal conduit 20A (FIG. 50). The regions where the conduit channels760A, 770A and 780A are closest to the outside diameter of externalconduit 20A unless reinforced tend to fail during high speed rotation.Having ribs parallel with the conduit channels beyond the anchor sleeveend 873A provides reinforcement to this region and prevents conduitfailure at high speed rotation. In one aspect, the ribs prevent thebuckling of the external conduit 20A in this region and act asstructural elements to transfer the torsional stress to the anchorsleeve 870A.

[0177] Connection sleeve 500A comprises body 830A having an upper sleeveend 831A and lower sleeve end 832A (FIGS. 46 and 47). Lower sleeve end832A has sleeve flange 790A and a plurality of protrusions 843A, whichare sized to engage indentations 484A on the wall surface 482482A oflumen connector 481A. When the bowl 10A is assembled, a fluid tight sealmay be provided by placing o-ring 791A around body 830A and compressingthe o-ring 791A between flange 790A and housing 100A. Upper sleeve end831A is adapted to be secured to external conduit 20A. Referring to FIG.46, 39A and 39B, connection sleeve 500A is secured to bowl 10A by meansof sleeve flange 790A and is adapted to fluidly connect conduit channels780A, 760A, 770A of external conduit 20A to bowl channels 420A and 410A,and chamber 740A of bowl 10A. When assembled, connection sleeve 500A ismounted to lumen connector 481A (FIGS. 39A and 39B).

[0178] Connection sleeve 500A preferably increases in diameter fromupper sleeve end 831A to lower sleeve end 832A and is overmolded tofirst conduit end 861A of external conduit 20A. Connection sleeve 500Aconnects bowl 10A to external conduit 20A without use of a rotatableseal, which would otherwise normally be located between bowl 10A andconnection sleeve 500A. The seal-less connection between bowl 10A andconnection sleeve 500A may occur as explained above or alternativelythrough use of, for example, an O-ring, a groove, or lip, grommet-typeconnection, welding, or a tight fit with or without adhesive in eitherbowl 10A or connection sleeve 500A.

[0179] As illustrated in FIG. 46 and 39B, sleeve flange 790A has abottom surface 847A that contacts with top surface 482A of lumenconnector 481A forming a tight seal. However, lumen connector 481A has aplurality of indentation 483A that provides for fluid communicationbetween separation chamber 220A and bowl chamber 740A, which, in turnhas fluid communication with conduit channel 770A. Bowl chamber 740A isdefined by lumen mounting recess 851A and top surface 482A of lumenconnector 481A, excluding the space occupied by hollow cylinders 321Aand 322A. A plurality of protrusions 843A on the bottom surface 847A ofsleeve flange 790A engages and slides into indentations 484A on the wallsurface 482B of lumen connector 481A, thus providing a tight fit.

[0180] Connection sleeve 500A helps to secure external conduit 20A tobowl 10A, thus fluidly connecting external conduit 20A to bowl 10A. Thisfluid connection enables fluid 800 to be supplied through externalconduit 20A to bowl 10A. Similarly, this fluid connection also enablesseparated fluid components b, 820 to be removed from bowl 10A throughexternal conduit 20A.

[0181] External conduit 20A has an approximately constant diameter whichhelps to reduce the rigidity. An excessively rigid external conduit 20Awill heat up and fail more quickly. Additionally, a constant diameterconduit is cheap/easy to manufacture, allows easy experimentation withconnection sleeve 500A and anchor sleeve 870A sizes, and allows bearingrings 871A, 872A to be easily slid thereon. Preferably the movement ofbearings 871A and 872A will be constrained by first and second shoulders882A and 884A. External conduit 20A may be made of any type of flexibletubing (such as medical tubing) or other such device providing a sealedpassageway for the flow of fluids, which may be pressurized, into or outof a reservoir of any sort, and which preferably can be disposable andsterilizable.

[0182] II. Permanent Tower System

[0183]FIG. 17 illustrates tower system 2000. Tower system 2000 is thepermanent (i.e., non-disposable) piece of hardware that receives thevarious devices of photopheresis kit 1000, such as, cassette 1100,irradiation chamber 700, and centrifuge bowl 10 (FIG. 1). Tower system2000 performs the valving, pumping, and overall control and drive offluid flow through disposable photopheresis kit 1000. Tower system 2000performs all of the necessary control function automatically through theuse of a properly programmed controller, for example a processor or ICcircuit, coupled to all of the necessary components. While a newdisposable kit must be discarded after each photopheresis therapysession, tower system 2000 is used over and over again. Tower system2000 can be modified to perform a number of extracorporeal blood circuittreatments, for example apheresis, by properly programming thecontroller or by changing some of its components.

[0184] Tower system 2000 has a housing having an upper portion 2100 anda base portion 2200. Base portion 2200 has a top 2201 and a bottom 2202.Wheels 2203 are provided at or near the bottom 2202 of base portion 2200so that tower system 2000 is mobile and can easily be moved from room toroom in a hospital setting. Preferably, the front wheels 2203 arepivotable about a vertical axis to allow ease in steering andmaneuvering tower system 2000. Top 2201 of base portion 2200 has a topsurface 2204 having control deck 1200, best illustrated in FIG. 22,built therein (see FIG. 22). In FIG. 17, cassette 1100 is loaded ontocontrol deck 1200. Base portion 2200 also has hooks (not illustrated),or other connectors, to hang plasma collection bag 51 and treatment bag50 therefrom. Such hooks can be located anywhere on tower system 2000 solong as their positioning does not interfere with the functioning of thesystem during therapy. Base portion 2200 has photoactivation chamber 750(FIG. 18) located behind door 751. Additional hooks (not illustrated)are provided on tower system 2000 for hanging saline and anticoagulantbags. Preferably, these hooks are located on upper portion 2100.

[0185] Photoactivation chamber 750 (FIG. 18) is provided in base portion2200 of tower system 2000 between top 2201 and bottom 2202 behind door751. Door 751 is hingedly connected to base portion 2200 and is providedfor access to photoactivation chamber 750 and to allow the operator toclose photoactivation chamber 750 so that UV light does not escape intothe surrounding during treatment. Recess 752 is provided to allow tubes1112, 1117 (FIG. 1) to pass into photoactivation chamber 750 whenirradiation chamber 700 is loaded and when door 751 is closed. Thephotoactivation chamber is discussed in detail below with respect toFIGS. 16 and 18.

[0186] Upper portion 2100 is located atop base portion 2200. Centrifugechamber 2101 (FIG. 19) is located in upper portion 2100 behindcentrifuge chamber door 2102. Centrifuge chamber door 2102 has a window2103 so an operator can see in centrifuge chamber 2101 and monitor forany problems. Window 2103 is constructed with glass thick enough towithstand any forces that may be exerted on it from an accident duringcentrifugation which can rotate the centrifuge bowl at speeds greaterthan 4800 RPMs. Preferably, window 2103 is constructed of shatter-proofglass. Door 2102 is hingedly connected to upper portion 2100 and has anautomatic locking mechanism that is activated by the system controllerduring system operation. Centrifuge chamber 2101 is discussed below inmore detail with respect to FIG. 19.

[0187] Preferably, deck 1200 is located on top surface 2204 of baseportion 2200 at or near the front of system tower 2000 while upperportion 2100 is extending upward from base portion 2200 near the rear oftower system 2000. This allows the operator easy access to control deck1200 while simultaneously affording the operator access to centrifugechamber 2101. By designing tower system 2000 to have the centrifugechamber 2101 in the upper portion 2100 and having the photoactivationchamber 750 and deck 1200 in base portion 2200, an upright configurationis achieved. As such, system tower 2000 has a reduced footprint size andtakes up a reduced amount of valuable hospital floor space. The heightof system tower 2000 remains below sixty inches so that one view is notobstructed when transporting the machine around the hospital form therear. Additionally, having deck 1200 in a fairly horizontal positionwill provide the operator with a place to set devices of photopheresiskit 1000 during the loading of other devices, facilitating easy loading.Tower system 2000 is robust enough to withstand forces and vibrationsbrought on by the centrifugation process.

[0188] A monitor 2104 is provided on centrifuge chamber door 2102 abovewindow 2103. Monitor 2104 has a display area 2105 for visuallydisplaying data to an operator, such as, for example, user interfacesfor data entry, loading instructions, graphics, warnings, alerts,therapy data, or therapy progress. Monitor 2104 is coupled to andcontrolled by the system controller. A data card receiving port 2001 isprovided on a side of monitor 2104. Data card receiving port 2001 isprovided to slidably receive data card 1195 which is supplied with eachdisposable photopheresis kit 1000 (FIG. 1). As mentioned above, datacard 1195 can be pre-programmed to store serve a variety of data tosupply to the system controller of tower system 2000. For example, datacard 1195 can be programmed to relay information so that the systemcontroller can ensure: (1) that the disposable photopheresis kit iscompatible with the blood drive equipment into which it is being loaded;(2) that the photopheresis kit is capable of running the desiredtreatment process; (3) that the disposable photopheresis kit is of acertain brand name or make. Data card receiving port 2001 has thenecessary hardware and circuitry to both read data from, and write datato, data card 1195. Preferably, data card receiving port 2201 willrecord treatment therapy data to data card 1195. Such information caninclude for example, collection times, collection volumes, treatmenttimes, volumetric flow rates, any alarms, malfunctions, disturbances inthe process, or any other desired data. While data card receiving port2001 is provided on monitor 2104, it can be located anywhere on towersystem 2000 so long as it is coupled to the system controller or otherappropriate control means.

[0189] A. Photoactivation Chamber for Receiving Irradiation Chamber

[0190] Referring now to FIGS. 16 and 18, photoactivation chamber 750 isillustrated in cross section. Photoactivation chamber 750 is formed byhousing 756. Housing 756 fits within base portion 2200 of tower system2000 behind door 751 (FIG. 17). Photoactivation chamber 750 has aplurality of electrical connection ports 753 provided on back wall 754.Electrical connection ports 753 are electrically coupled to a source ofelectrical energy. Photoactivation chamber 750 is designed to receiveUVA light assembly 759 (FIG. 16). When fully loaded into photoactivationchamber 750, electrical contacts (not illustrated) located on contactwall 755 of UVA light assembly 759 form an electrical connection withelectrical connection ports 753. This electrical connection allowselectrical energy to be supplied to UVA lamps 758 so that they can beactivated. Preferably, three electrical connection ports are providedfor each set of UVA lamps 758. More preferably, UVA light assembly 759has two sets of UVA lamps 758 forming a space which irradiation chamber700 can be inserted. The supply of electrical energy to UVA lamps 758 iscontrolled by the properly programmed system controller using a switch.UVA lamps 758 are activated and deactivated as necessary by thecontroller during the photopheresis therapy session.

[0191] Vent hole 757 is provided in the top of housing 756 near backwall 754 of photoactivation chamber 750. Vent hole 757 connects to ventduct 760 which leads out of the back of tower system 2000. When heatgenerated by UVA lamps 758 builds up in photoactivation chamber 750during a treatment therapy, this heat escapes photoactivation chamber750 via vent hole 757 and vent duct 760. The heat exits tower system2000 through tower housing hole 761 located in the rear of tower system2000, away from the patient and the operator.

[0192] Photoactivation chamber 750 further comprises tract 762 forreceiving irradiation chamber 700 and holding irradiation in an uprightposition between UVA lamps 758. Tract 762 is at or near the bottom ofphotoactivation chamber 750. Preferably, a leak detector circuit 763 isprovided below tract 762 to detect any fluid leaks irradiation chamber700 during, before, or after operation. Leak detector circuit 762 hastwo electrodes patterned in a U shape located on an adhesive backed flexcircuit. The electrodes are designed to allow for application of a shortcircuit to test for discontinuities. One end of each electrode goes toan integrated circuit while the other end of each electrode is tied to asolid-state switch. The solid-state switch can be used to check forcontinuity of the electrodes. By closing the switch the electrodes areshorted to one another. The integrated circuit then detects the short.Closing the switch causes a situation equivalent to the electrodesgetting wet (i.e., a leak). IN If the electrodes are damaged in any way,the continuity check will fail. This is a positive indication that theelectrodes are not damaged. This test can be performed each time atsystem start-up or periodically during normal operation to ensure thatleak detection circuit 762 is working properly. Leak detection circuit762 helps ensure that leaks do not go unnoticed during an entire therapysession because the leak detection circuit is damaged. An electricalschematic of leak detector circuit 762 is provided in FIG. 20.

[0193] B. Centrifuge Chamber

[0194]FIG. 19 illustrates centrifuge chamber 2101 in cross section withthe housing of tower system 2000 removed. Rotational device 900 (also incross-section) capable of utilizing 1-omega 2-omega spin technology ispositioned within centrifuge chamber 2101. Rotational device 900includes a rotating bracket 910 and a bowl holding plate 919 forrotatably securing centrifuge bowl 10 (FIG. 1). Housing 2107 ofcentrifuge chamber 2101 is preferably made of aluminum or some otherlightweight, sturdy metal. Alternatively, other rotational systems maybe used within tower system 2000 such as that described in U.S. Pat. No.3,986,442, which is expressly incorporated herein by reference in itsentirety.

[0195] Leak detection circuit 2106 is provided on back wall 2108 ofhousing 2107. Leak detection circuit 2106 is provided to detect anyleaks within centrifuge bowl 10 or the connecting tubes duringprocessing. Leak detection circuit 2106 is identical to leak detectorcircuit 762 described above. An electrical schematic of leak detectioncircuit 2106 is provided in FIG. 21.

[0196] C. Fluid Flow Control Deck

[0197]FIG. 22 illustrates control deck 1200 of tower system 2000 (FIG.17) without a cassette 1100 loaded thereon. Control deck 1200 performsthe valving and pumping so as to drive and control fluid flow throughoutphotopheresis kit 1000. Preferably, deck 1200 is a separate plate 1202that is secured to base portion 2200 of tower system 2000 via screws orother securing means, such as, for example, bolts, nuts, or clamps.Plate 1202 can be made of steel, aluminum, or other durable metal ormaterial.

[0198] Deck 1200 has five peristaltic pumps, whole blood pump 1301,return pump 1302, recirculation pump 1303, anticoagulant pump 1304, andred blood cell pump 1305 extending through plate 1202. Pumps 1301-1305are arranged on plate 1202 so that when cassette 1100 is loaded ontodeck 1200 for operation, pump loop tubes 1120-1124 extend over andaround pumps 1301-1305 (FIG. 25).

[0199] Air bubble sensor assembly 1204 and HCT sensor assembly 1205 areprovided on plate 1202. Air bubble sensor assembly 1204 has threetrenches 1206 for receiving tubes 1114, 1106, and 1119 (FIG. 25). Airbubble sensor assembly 1204 uses ultrasonic energy to monitor tubes1114, 1106, and 1119 for differences in density that would indicate thepresence of air in the liquid fluids normally passing therethrough.Tubes 1114, 1106, and 1119 are monitored because these lines go to thepatient. Air bubble sensor assembly 1204 is operably coupled andtransmits data to the system controller for analysis. If an air bubbleis detected, the system controller will shut down operation and prohibitfluid flow into the patient by occluding tubes 1114, 1106, and 1109 bymoving compression actuators 1240-1242 to a raised position, therebycompressing tubes 1114, 1106, and 1119 against cassette 1100 asdiscussed above and/or shutting down the appropriate pump. HCT sensorassembly 1205 has trench 1207 for receiving HCT component 1125 of tube1116. HCT sensor assembly 1205 monitors tube 1116 for the presence ofred blood cells by using a photoelectric sensor. HCT sensor assembly1205 is also operably coupled to and transmits data to the systemcontroller. Upon HCT sensor assembly 1205 detecting the presence of redblood cells in tube 1116, the system controller will take theappropriate action, such as stopping the appropriate pump or activatingone of compression actuators 1243-1247, to stop fluid flow through tube1116.

[0200] Deck 1200 also has five compression actuators 1243-1247 and threecompression actuators 1240-1242 strategically positioned on plate 1202so that when cassette 1100 is loaded onto deck 1200 for operation, eachof compression actuators 1240-1247 are aligned with correspondingapertures 1137 and 1157. Compression actuators 1240-1247 can be movedbetween a lowered position and a raised position. As illustrated in FIG.22, compression actuators 1243-1247 are in the lowered position andcompression actuators 1240-1242 are in the raised position. When in araised position, and when cassette 1100 is loaded onto deck 1200 asillustrated in FIG. 25, compression actuators 1240-1247 will extendthrough the corresponding apertures 1137 or 1157 and compress theportion of flexible tubing that is aligned with that aperture, therebypinching the flexible tube shut so that fluid can not pass. When in thelowered position, compression actuators 1240-1247 do not extend throughapertures 1137 and 1157 and thus do compress the flexible tubing.

[0201] Compression actuators 1243-1247 are spring retracted so thattheir default position is to move to the lowered position unlessactivated. Compression actuators 1243-1247 are independently controlledand can be raised r lowered independent of one another. Compressionactuators 1240-1242 on the other hand are coupled together. As such,when one compression actuator 1240-1242 is lowered or raised, the othertwo compression actuators 1240-1242 are also lowered in raisedaccordingly. Additionally, compression actuators 1240-1242 are springloaded so that their default position is to move to the raised position.Thus, if the system loses power during a therapy session, compressionactuators 1240-1242 will automatically move to the raised position,occluding tubes 1114, 1106, and 1119 and preventing fluids from enteringor leaving the patient.

[0202] Referring now to FIGS. 23 and 24, deck 1200 further includessystem controller 1210, cylinder assembly 1211, manifold assemblies1213, pump cable 1215, pump motor cable 1216, and timing belt assembly1217. System controller 1210 is a properly programmed integrated circuitthat is operably coupled to the necessary components of the system toperform all of the functions, interactions, decisions, and reactiondiscussed above and necessary to perform a photopheresis therapyaccording to the present invention. Cylinder assembly 1211 couples eachof compression actuators 1240-1247 to a pneumatic cylinder. Air ports1212 are provided on the various elements of deck 1200 as necessary toconnect air lines to the devices and the appropriate one of manifolds1213. As such, air can be provided to the devices as necessary toactuate the necessary component, such as compression valves 1240-1247.All of these functions and timing are controlled by system controller1210. Timing belt assembly 1217 is used to coordinate the rotation ofrotating clamps 1203. Finally, plate 1202 includes a plurality of holes1215, 1219, 1220, 1221, and 1218 so that the various components of deck1200 can be properly loaded into and so that deck 1200 can be secured totower system 2000. Specifically, pumps 1301-1305 fit into holes 1314,HCT sensor assembly 1205 fits into hole 1220, air bubble detectorassembly 1204 fits into hole 1219, compression actuators 1240-1247extend through holes 1218, and bolts extend through holes 1221 to securedeck 1200 to tower assembly 2000.

[0203] 1. Cassette Clamping Mechanism

[0204] Referring now to FIGS. 22 and 25, the method by which cassette1100 is loaded and secured to deck 1200 will now be discussed. In orderfor system 2000 to perform a photopheresis therapy, cassette 1100 mustbe properly loaded onto deck 1200. Because of the compression actuatorvalving system incorporated in the present invention, it is imperativethat cassette 1100 be properly secured to deck 1200 and not shift orbecome dislodged when compression actuators 1240-1247 occlude portionsof the flexible tubing by compressing the flexible tubing against cover1130 of cassette 1100 (FIG. 3). However, this requirement competes withthe desired goals of ease in loading cassette 1100 onto deck 1200 andreducing operator errors. All of these goals are achieved by the belowdescribed cassette clamping mechanism.

[0205] In order to facilitate clamping of cassette 1100 to deck 1200,deck 1200 is provided with two catches 1208 and two rotating clamps 1203and 1223. Catches 1208 have a slot 1228 near the middle of the topplate. Catches 1208 are secured to plate 1202 at predetermined positionsso that the spacing between them is substantially the same as thespacing between tabs 1102 and 1103 on cassette 1100 (FIG. 2). Rotatingclamps 1203 and 1223 are illustrated in a closed position. However,rotating clamps 1203 and 1223 can be rotated to an open position (notillustrated) manually or through the automatic actuation of a pneumaticcylinder. Rotating clamps 1203 and 1223 are spring loaded by torquesprings so as to automatically return to the closed position whenadditional torque is not being applied. Rotating clamps 1203 and 1223are linked together by timing belt assembly 1217 (FIG. 24).

[0206] Referring now to FIG. 23, timing belt assembly 1217 comprisestiming belt 1226, torque spring housings 1224, and tension assembly1225. Timing belt assembly 1217 coordinates the rotation of rotationalclamps 1203 and 1223 so that if one is rotated, the other also rotatesin the same direction and the same amount. In other words, rotationalclamps 1203 and 1223 are coupled. Tension assembly 1217 ensures thattiming belt 1226 is under sufficient tension to engage and rotate therotational clamp 1203 or 1223 that is being coordinated. Torque springhousings 1224 provide casings for the torque springs that torquerotational clamps 1203 and 1223 to the closed position.

[0207] Referring back to FIGS. 22 and 25, when loading cassette 1100onto deck 1200, cassette 1100 is placed at an angle to deck 1200 andtabs 1102 and 1103 (FIG. 2) are aligned with catches 1208. Cassette 1100is moved so that tabs 1102 and 1103 slidably insert into catches 1208.Rotational clamps 1203 and 1223 are in the closed position at this time.The rear of the cassette 1100 (i.e. the side opposite the tabs 1102 and1103) contacts rotational clamps 1203 and 1223 as tabs 1102 and 1103 arebeing inserted in catches 1108. As force is applied downward on cassette1100, rotational clamps 1103 and 1123 will be rotated to the openposition, allowing the rear of cassette 1100 to move downward to aposition below ledges 1231 of rotational clamps 1203 and 1223. Oncecassette 1100 is in this position, the rotational clamps 1203 and 1223spring back from the force applied by the torque springs and rotate backto the closed position, locking cassette 1100 in place. When in thelocked position, cassette 1100 can resist upward and lateral forces.

[0208] To remove cassette 1110 after the therapy session is complete,rotational clamps 1203 and 1223 are rotated to the open position eithermanually or automatically. Automatic rotation is facilitated by an aircylinder that is coupled to an air line and system controller 1210. Oncerotational clamps 1203 and 1223 are in the open position, cassette 1100is removed by simple lifting and sliding tabs 1102 and 1103 out ofcatches 1208.

[0209] 2. Self-Loading Peristaltic Pumps

[0210] Referring to FIG. 24, peristaltic pumps 1301-1305 are provided ondeck 1200 and are used to drive fluids through photopheresis kit 1000(FIG. 1) along desired pathways. The activation, deactivation, timing,speed, coordination, and all other functions of peristaltic pumps1301-1305 are controlled by system controller 1210. Peristaltic pumps1301-1305 are identical in structure. However, the placement of eachperistaltic pump 1301-1305 on deck 1200 dictates the function of eachperistaltic pump 1301-1305 with respect to which fluid is being drivenand along which pathway. This is because the placement of peristalticpumps 1301-1305 dictates which pump loop 1220-1224 will be loadedtherein.

[0211] Referring now to FIGS. 28 and 29, whole blood pump 1301 isillustrated in detail. The structure and functioning of whole blood pumpwill be described with the understanding that peristaltic pumps1302-1305 are identical. Whole blood pump 1301 has motor 1310, positionsensor 1311, pneumatic cylinder 1312, pneumatic actuator 1313, rotor1314 (best illustrated in FIG. 30), and housing 1315.

[0212] Rotor 1314 is rotatably mounted within housing 1315 and is inoperable connection with drive shaft 1316 of motor 1310. Specifically,rotor 1314 is mounted within curved wall 1317 of housing 1315 so as tobe rotatable by motor 1310 about axis A-A. When rotor 1314 is mounted inhousing 1315, a space 1318 exists between rotor 1314 and curved wall1317. This space 1318 is the tube pumping region of whole blood pump1301 into which pump loop tube 1121 (FIG. 33) fits when loaded forpumping. Position sensor 1316 is coupled to drive shaft 1316 of motor1310 so that the rotational position of rotor 1314 can be monitored bymonitoring drive shaft 1316. Position sensor 1311 is operably connectedand transmits data to system controller 1210 (FIG. 24). By analyzingthis data, system controller 1210, which is also coupled to motor 1310,can activate motor 1310 to place rotor 1314 in any desired rotationalposition.

[0213] Housing 1315 also includes a housing flange 1319. Housing flange1319 is used to secure whole blood pump 1310 to plate 1202 of deck 1200(FIG. 22). More specifically, a bolt is extended through bolt holes 1320of housing flange 1319 to threadily engage holes within plate 1202.Housing flange 1319 also includes a hole (not shown) to allow pneumaticactuator 1313 to extend therethrough. This hole is sized so thatpneumatic actuator 1313 can move between a raised and lowered positionwithout considerable resistance. Pneumatic actuator 1313 is activatedand deactivated by pneumatic cylinder 1312 in a piston-like mannerthrough the use of air. Pneumatic cylinder 1312 comprises air inlet hole1321 for connecting an air supply line. When air is supplied topneumatic cylinder 1312, pneumatic actuator extends upward throughhousing flange 1319 to a raised position. When air ceases to be suppliedto pneumatic cylinder 1312, pneumatic actuator retracts back intopneumatic cylinder 1312, returning to the lowered position. Systemcontroller 1210 (FIG. 22) controls the supply of air to air inlet hole1321.

[0214] Curved wall 1317 of housing 1315 contains two slots 1322 (onlyone visible). Slots 1322 are located on substantially opposing sides ofcurved wall 1317. Slots 1322 are provided for allowing pump loop tube1121 (FIG. 33) to pass into tube pumping region 1318. More specifically,pump inlet portion 1150 and outlet portions 1151 (FIG. 33) of pump looptube 1121 pass through slots 1322.

[0215] Turning now to FIGS. 30 and 31, rotor 1314 is illustrated asremoved from housing 1315 so that its components are more clearlyvisible. Rotor 1314 has a top surface 1323, angled guide 1324, rotorflange 1325, two guide rollers 1326, two drive rollers 1327, and rotorfloor 1328. Guide rollers 1326 and drive rollers 1327 are rotatablysecured about cores 1330 between rotor floor 1328 and a bottom surface1329 of rotor flange 1325. As is best illustrated in FIG. 29, cores 1330fit into holes 1331 of rotor floor 1328 and recesses 1332 in bottomsurface 1329. Guide rollers 1326 and drive rollers 1327 fit around cores1330 and can rotate thereabout. Preferably, two guide rollers 1326 andtwo drive rollers 1327 are provided. More preferably, guide rollers 1326and drive rollers 1327 are provided on rotor 1314 so as to be in analternating pattern.

[0216] Referring to FIGS. 29 and 31, drive rollers 1327 are provided tocompress the portion of pump loop tube 1121 that is loaded into tubepumping region 1318 against the inside of curved wall 1317 as rotor 1314rotates about axis A-A, thereby deforming the tube and forcing fluids toflow through the tube. Changing the rotational speed of rotor 1314 willcorrespondingly change the rate of fluid flow through the tube. Guiderollers 1326 are provided to keep the portion of pump loop tube 1121that is loaded into tube pumping region 1318 properly aligned duringpumping. Additionally, guide rollers 1326 help to properly load pumptube loop 1121 into tube pumping region 1318. While guide rollers 1326are illustrated as having a uniform cross-section, it is preferred thatthe top plate of the guide rollers be tapered so as to come to a sharperedge near its outer diameter. Tapering the top plate results in a guideroller with a non-symmetric cross-sectional profile. The taperedembodiment helps ensure proper loading of the tubing into the tubepumping region.

[0217] Rotor 1314 further includes cavity 1328 extending through itscenter. Cavity 1328 is designed to connect rotor 1314 to drive shaft1316 of motor 1310.

[0218] Referring now to FIGS. 30 and 32, rotor flange has opening 1333.Opening 1333 is defined by a leading edge 1334 and a trailing edge 1335.The terms leading and trailing are used assuming that rotating rotor1314 in the clockwise direction is the forward direction while rotatingrotor 1314 in a counterclockwise direction is the rearward direction.However, the invention is not so limited and can be modified forcounterclockwise pumps. Leading edge 1334 is beveled downward intoopening 1333. Trailing edge 1335 extends upward from the top surface ofrotor flange 1325 higher than the leading edge 1334. Leading edge isprovide for trailing edge for capturing and feeding pump loop tube 1121into tube pumping region 1318 upon rotor 1314 being rotated in theforward direction.

[0219] Rotor 1314 also has angled guide 1324 extending upward, at aninverted angle, from rotor flange 1325. Angled guide 1324 is providedfor displacing pump loop tube 1121 toward rotor flange 1325 upon rotor1314 being rotated in the forward direction. Preferably, angled guide1324 has elevated ridge 1336 running along top surface 1323 for manualengagement by an operator if necessary. More preferably, angled guide1314 is located forward of leading edge 1334.

[0220] Referring now to FIGS. 28 and 33, whole blood pump 1301 canautomatically load and unload pump lop tube 1121 into and out of tubepumping region 1318. Using position sensor 1311, rotor 1314 is rotatedto a loading position where angled guide 1324 will face cassette 1100when cassette 1100 is loaded onto deck 1200 (FIG. 25). Morespecifically, rotor 1314 is preset in a position so that angled guide1324 is located between inlet portion 1150 and outlet portion 1151 ofpump loop 1121 when cassette 1100 is secured to the deck, as isillustrated in FIG. 13. When cassette 1100 is secured to deck 1200, pumplop tube 1121 extends over and around rotor 1314. Pneumatic actuator1313 is in the lowered position at this time.

[0221] Once cassette 1100 is properly secured and the system is ready,rotor 1314 is rotated in the clockwise direction (i.e., the forwarddirection). As rotor 1314 rotates, pump tube loop 1121 is contacted byangled guide 1324 and displaces against the top surface of rotor flange1325. The portions of pump loop tube 1121 that are displaced againstrotor flange 1325 are then contacted by trailing edge 1325 and feddownward into tube pumping region 1318 through opening 1333. A guideroller 1326 is provided directly after opening 1333 to further properlyposition the tubing within tube pumping chamber for pumping by driverollers 1327. When loaded, inlet portion 1150 and outlet portion 1151 ofpump loop tube 1121 pass through slots 1322 of curved wall 1317. One anda half revolutions are needed to fully load the tubing.

[0222] To automatically unload pump tube loop 1121 from whole blood pump1301 after the therapy is complete, rotor 1314 is rotated to a positionwhere opening 1333 is aligned with the slot 1322 through which outletportion 1151 passes. Once aligned, pneumatic actuator 1313 is activatedand extended to the raised position, contacting and lifting outletportion 1151 to a height above trailing edge 1335. Rotor 1314 is thenrotated in the counterclockwise direction, causing trailing edge to 1335to contact and remove pump loop tube 1121 from tube pumping region 1318via opening 1333.

[0223] D. Infra-Red Communication

[0224] Referring to FIG. 34, tower system 2000 (FIG. 17) preferablyfurther includes a wireless infrared (“IR”) communication interface (notshown). The wireless IR interface consists of three primary elements,system controller 1210, IRDA protocol integrated circuit, 1381, and IRDAtransceiver port 1382. The IR communication interface is capable of bothtransmitting and receiving data via IR signals from a remote computer orother device having IR capabilities. In sending data, system controller1210 sends serial communication data to the IRDA protocol chip 1381 tobuff the data. IRDA protocol chip 1381 adds additional data and othercommunication information to the transmit string and then sends it toERDA transceiver 1382. Transceiver 1382 converts the electrical transmitdata into encoded light pulses and transmits them to a remote device viaa photo transmitter.

[0225] In receiving data, IR data pulses are received by a photodetector located on the transceiver chip 1382. The transceiver chip 1382converts the optical light pulses to electrical data and sends the datastream to IRDA protocol chip 1381 where the electrical signal isstripped of control and additional IRDA protocol content. The remainingdata is then sent to the system controller 1210 where the data stream isparsed per the communication protocol.

[0226] By incorporating an IR communication interface on tower system2000 real time data relating to a therapy session can be transmitted toa remote device for recording, analysis, or further transmission. Datacan be sent via IR signals to tower system 2000 to control the therapyor allow protocols to be changed in a blinded state. Additionally, IRsignals do not interfere with other hospital equipment, like otherwireless transmission methods, such as radio frequency.

[0227] III. Photopheresis Treatment Process

[0228] Referring together to FIG. 26, a flow chart illustrating anembodiment of the invention which includes photactivation of buffy coat,and FIG. 27, a schematic representation of apparatus which can beemployed in such an embodiment, the process starts 1400 with a patient600 connected by means of a needle adapter 1193 carrying a needle, fordrawing blood, and needle adapter 1194 carrying another needle, forreturning treated blood and other fragments. Saline bag 55 is connectedby connector 1190 and anticoagulant bag 54 is connected by connector1191. Actuators 1240, 1241, and 1242 are opened, anticoagulant pump 1304is turned on, and saline actuator 1246 is opened so that the entiredisposable tubing set is primed 1401 with saline 55 and anticoagulant54. The centrifuge 10 is turned on 1402, and blood-anticoagulant mixtureis pumped 1403 to the centrifuge bowl 10, with the A/C pump 1304 and WBpump 1301 controlled at a 1:10 speed ratio.

[0229] When the collected volume reaches 150 ml 1404, the return pump1302 is set 1405 at the collection pump 1301 speed until red cells aredetected 1406 at an HCT sensor (not shown) in the centrifuge chamber1201 (FIG. 19). Packed red cells and buffy coat have at this pointaccumulated in the spinning centrifuge bowl and are pumped out slowly ata rate, controlled by the processor, which maintains the red cell lineat the sensor interface level.

[0230] The red cell pump 1305 is then set 1407 at 35% of the inlet pumpspeed while controlling 1408 the rate to maintain the cell line at theinterface level until the collection cycle volume is reached 1409, atwhich point the red cell pump 1305 is turned off 1410 and the fluid pathto the treatment bag 50 via the HCT sensor 1125 is opened by loweringactuator 1244, and stops when the HCT sensor 1125 detects 1411 redcells. “Collection cycle volume” is defined as the whole blood processedtarget divided by the number of collection cycles, for example a whiteblood process target of 1500 ml may require 6 cycles, and so 1500/6 is avolume of 250 ml. With whole blood continuing at 1410 to be deliveredfrom the patient to the bowl and the red cell pump off, red cells willaccumulate and will push out the buffy coat from inside the bowl 10. Thered cells are used to push out the buffy coat and will be detected bythe effluent hematocrit (HCT) sensor, indicating that the buffy coat hasbeen collected.

[0231] If another cycle is needed 1412, the centrifuge 10 effluent pathis returned 1413 to the plasma bag 51 and the red cell pump 1305 rate isincreased 1413 to the inlet pump 1301 pump rate until red cells aredetected 1414, which is the beginning of the second cycle. If anothercycle 1412 is not needed, the centrifuge 10 is turned off 1415 and inletpump 1301 and anticoagulant pump 1304 are set at KVO rate, 10 ml/hr inthis embodiment. The effluent path is directed 1416 to the plasma bag51, the red cell pump 1305 rate is set 1417 at 75 ml/min, therecirculation pump 1303 and photoactivation lamps are turned on 1418 forsufficient period to treat the buffy coat, calculated by the controllerdepending on the volume and type of disease being treated.

[0232] When the bowl 10 is empty 1419, the red cell pump 1305 is turnedoff 1420 and the plasma bag 51 is emptied 1421 by opening actuator 1247and continuing return pump 1302. The return pump 1302 is turned off 1422when the plasma bag 51 is empty and when photoactivation is complete1423, the treated cells are returned 1424 to the patient from the plate700 by means of the return pump 1302. Saline is used to rinse the systemand the rinse is returned to the patient, completing the process 1425.

[0233] The anticoagulant, blood from patient, and fluid back to patientare all monitored by air detectors 1204 and 1202, and the fluid back tothe patient goes through drip chamber and filter 1500. The pumps, 1304,1301, 1302, 1303, and 1305, the actuators 1240, 1241, 1242, 1243, 1244,1245, 1246, and 1247, and the spinning of the bowl 10 are all controlledby the programmed processor in the tower.

[0234] The process and related apparatus have significant advantagesover prior processes and apparatus in that the invention allow buffycoat to be in the bowl longer since red cells are being drawn off whilecollecting buffy coat in the bowl while centrifuging, keeping more buffycoat in the bowl until the desired amount of buffy coat cells arecollected prior to withdrawing the collected buffy cells. Platelets,leukocytes, and other buffy coat fractions can also be separated, or redcells can be collected rather than returning them with plasma to thepatient as the illustrated process does.

[0235] It has been found that increasing the time that buffy coat 810 issubjected to rotational motion in centrifuge bowl 10 yields a “cleanercut” of buffy coat 820. A “cleaner cut” means that the hematocrit count(HCT %) is decreased. HCT % is the amount of red blood cells present pervolume of buffy coat. The amount of time that buffy coat 820 issubjected to rotational motion in centrifuge bowl 10 can be maximized inthe following manner. First, whole blood 800 is fed into first bowlchannel 420 as centrifuge bowl 10 is rotating. As discussed above, wholeblood 800 is separated into buffy coat 820 and RBC's 810 as it movesoutwardly atop lower plate 300. Second bowl channel 410 and third bowlchannel 740 are closed at this time. The inflow of whole blood 800 iscontinued until the separation volume 220 is filled with a combinationof buffy coat 820 near the top and RBC's 810 near the bottom ofcentrifuge bowl 10. By removing RBC's 810 from centrifuge bowl 10 viasecond bowl channel 410 only, additional volume is created for theinflow of whole blood 800 and the unremoved buffy coat 820 is subjectedto rotational forces for an extended period of time. As centrifuge bowl10 continues to rotate, some of the RBC's 810 that may be trapped inbuffy coat 820 get pulled to the bottom of centrifuge bowl 10 and awayfrom third bowl channel 740 and buffy coat 820. Thus, when third bowlchannel 740 is opened, the buffy coat 820 that is removed has a lowerHCT %. By controlling the inflow rate of whole blood 800 and the outflowrates of buffy coat 820 and RBC's 810, a steady state can be reachedthat yields a buffy coat 820 with an approximately constant HCT %.

[0236] The elimination of batch processing and the improved yieldsachieved by the current invention, have reduced the treatment timenecessary to properly treat patients. For an average sized adult, 90-100milliliters of buffy coat/white blood cells must be captured in order toconduct a full photopheresis treatment. In order to collect this amountof buffy coat/white blood cells, the present invention needs to processaround 1.5 liters of whole blood. The required amount of buffycoat/white blood cells can be removed from the 1.5 liters of whole bloodin about 30-45 minutes using the present invention, collecting around60% or more of the total amount of the buffy coat/white blood cells thatare subjected to the separation process. The captured buffy coat/whiteblood cells have an HCT of 2% or less. In comparison, one existingapparatus, the UVAR XTS, takes around 90 minutes to process 1.5 litersof whole blood to obtain the sufficient amount of buffy coat/white bloodcells. The UVAR XTS only collects around 50% of the total amount of thebuffy coat/white blood cells that are subjected to the separationprocess. The HCT of the buffy coat/white blood cells collected by theUVAR XTS is around, but not substantially below, 2%. Another existingapparatus, the Cobe Spectra™ by Gambro, must process 10 liters of wholeblood in order to collect the sufficient amount of buffy coat/whiteblood cells. This typically takes around 150 minutes, collecting only10-15% of the total amount of the buffy coat/white blood cells that aresubjected to the separation process, and having an HCT of about 2%.Thus, it has been discovered that while existing apparatus and systemsrequire anywhere from 152 to 225 minutes to separate, process, treat,and reinfuse the requisite amount of white blood cells or buffy coat,the present invention can perform the same functions in less than 70minutes. These times do not include the patient preparation or primetime. The times indicate only the total time that the patient isconnected to the system.

What is claimed is:
 1. An apparatus for separating components of a fluidcomprising: an outer housing with an upper housing end and a lowerhousing end, wherein said outer housing increases in diameter from saidupper housing end to said lower housing end, said lower housing endhaving a housing floor and said housing upper end having a housingoutlet, said outer housing adapted for rotation about a center axis;said outer housing containing a core in said interior volume; the corehaving an outer wall, an upper core end, and a lower core end; said coreconnected with said outer housing for rotation therewith; and providinga separation volume between said core and said outer housing; said coreend having a lumen connector and a lumen connector top surface; a firstlumen for providing fluid communication from the housing outlet throughthe lumen connector and then radially outward through the core to thefluid separation volume; a second lumen providing fluid communicationsfrom the housing outlet extending axially along center axis to housingfloor; a connection sleeve which forms with the lumen connector achamber and provide fluid communications between the housing outlet andthe separation volume.
 2. An apparatus of claim 1 wherein said firstlumen extending radially out to outer housing about midway to saidhousing floor.
 3. An apparatus of claim 1 wherein said lumen extendingradially out to outer housing about midway to said housing floor throughone to eight channels.
 4. An apparatus of claim 1 wherein said outerwall of said top core increases in diameter from said upper end to saidlower end.
 5. An apparatus of claim 1 wherein connection sleeve isadapted to be secured to said apparatus near said housing outlet of saidouter housing for rotation therewith, said connection sleeve adapted tofluidly connect a first bowl channel, second bowl channels, and achamber.
 6. An apparatus for separating components of a fluidcomprising: an outer housing with an upper housing end and a lowerhousing end, wherein said outer housing increases in diameter from saidupper housing end to said lower housing end, said lower housing endhaving a housing floor and said housing upper end having a housingoutlet, said outer housing having an interior volume and adapted forrotation about a center axis; a top core having an outer wall, an uppertop core end, and a lower top core end; said top core connected withsaid outer housing for rotation therewith; occupying a top coaxialvolume of said interior volume of said outer housing; and providing atop separation volume between said top core and said outer housing; saidupper top core end having a lumen connector; said lumen connector havinga first lumen wall extending downward from the a top surface of thelumen connector; said lumen connector further having an inner lumen wallwithin said first lumen wall and extending downward from the topsurface; said inner lumen wall having a top wall end and a bottom wallend; an upper plate having a top surface, a bottom surface, a secondlumen wall extending above said top surface; said upper plate adapted toform a tight fit with the lower top core end for rotation therewith;said second lumen wall (402A) adapted to overlap with said first lumenwall (401A) to form a lumen (400A) having an upper lumen end (480A) anda lower lumen end (490A); said lumen (400A) extending axially throughsaid core 200A forming a first bowl channel (420A) for inflowing saidfluid (800) and said lumen (400A) having fluid communication withseparation volume (220A) via trench (305A); a bottom core (201A) havingan outer wall (211A), a top surface (309A) contacting and connected withbottom surface (297A) of upper plate (299A) for rotation therewith; anupper bottom core end (206A), a lower bottom core end (296A), said topsurface (309A) having an indentation (186A) and a trench (305A), and alumen wall (324A) that has an upper wall end (324C) and a lower wall end(324B); said bottom core occupying a bottom coaxial volume of saidinterior volume (710A) of said outer housing (100A); said upper wall end(324C) of lumen wall (324A) is adapted to engage with bottom wall end(325B) of inner lumen wall (325A) to form an inner lumen 400B having anupper lumen end (325C) and a lower lumen end (324B); said inner lumen(400B) forming a second bowl channel (410A) for removing a firstseparated fluid component (810); a lower plate (300A) having a topsurface (730A), a bottom surface (730B), and a hollow cylinder (320A)near center of lower plate (300A); said hollow cylinder (320A) has anopening (302A) adapted to engage with lower wall end (324B) of lumen(324A); and said lower plate (300A) having a circumference adapted toform a tight fit with the lower bottom core end (296A) for rotationtherewith; a connection sleeve having a sleeve flange surrounding alumen mounting recess; said lumen mounting recess and top surface oflumen connector engaged to form a bowl chamber for removing a secondseparated fluid component; said connection sleeve further adapted to besecured to said apparatus near said housing outlet of said outer housingfor rotation therewith.
 7. The apparatus of claim 6 wherein said outerwall (210A) of said top core (200A) increases in diameter from saidupper end (205A) to said lower end (295A).
 8. The apparatus of claim 6wherein said outer wall (211A) of said bottom core (201A) increases indiameter from said upper end (206A) to said lower end (296A).
 9. Theapparatus of claim 6 wherein said outer wall (210A) of said top core(200A) increases in diameter from said upper end (205A) to said lowerend (295A) and said outer wall (211A) of said bottom core (201A)increases in diameter from said upper end (206A) to said lower end(296A).
 10. The apparatus of claim 6 wherein lumen (400A) having aheight (404A) and lumen wall (324A) having a height (324F) and theheight (404A) of lumen (400A) is about one third to about four times theheight (324F) of lumen wall (324A).
 11. The apparatus of claim 10wherein the height (404A) of lumen (400A) and the height of lumen wall(324A) are about the same.
 12. The apparatus of claim 6 wherein the topsurface (309A) of bottom core (201A) has one to 10 trenches (305A). 13.The apparatus of claim 12 wherein the top surface (309A) of bottom core(201A) has three to six trenches (305A).
 14. The apparatus of claim 6wherein said connection sleeve (500A) adapted to fluidly connect a first(420A) and second (410A) bowl channels, and a bowl chamber (740A) to acorresponding conduit channel (760A, 770A, and 780A) of an externalconduit (20A).
 15. The apparatus of claim 6 wherein said outer housing(100A) comprises a locking mechanism adapted to secure said outerhousing (100A) to a means (900) for rotating said apparatus (10A). 16.The apparatus of claim 15 wherein said locking mechanism comprisesprotrusions (150A).
 17. The apparatus of claim 16 wherein said lockingmechanism comprises a key slot (160A).
 18. The apparatus of claim 6wherein said lower plate (300A) is circular.
 19. The apparatus of claim6 wherein said apparatus (10A) is adapted for use without a rotatableseal.
 20. The apparatus of claim 6 wherein said apparatus (10A) isclosed to undesired contagions.
 21. The apparatus of claim 6 whereinsaid apparatus (10A) is adapted to allow rotation of said cores (200A,201A), said lower plate (300A), said upper plate (299A), and said outerhousing (100A) about said lumens (400A, 400B).
 22. The apparatus ofclaim 6 further comprising means (900) for rotating said outer housing(100A) about said axis (11).
 23. The apparatus of claim 22 wherein saidmeans (900) for rotating comprises a bracket (910).
 24. The apparatus ofclaim 23 wherein said bracket (910) is adapted to engage and rotate anexternal conduit (20A) that is fluidly connected to said first bowlchannel (420A), said second bowl channel (410A), and said bowl chamber(740A).
 25. The apparatus of claim 24 wherein said rotation means (900)is adapted to rotate said outer housing (100A) and said external conduit(20A) using 1-omega/2-omega spin technology.
 26. The apparatus of claim22 further comprising: means (605) to remove said fluid (800) from asource (600), said means (605) to remove said fluid (800) fluidlyconnected to said first bowl channel (420A); means (607) to remove saidfirst separated fluid component (810) via said second bowl channel(410A); means (608) to remove said second separated fluid component(820) via said bowl chamber (740A); and means (609) to treat said secondseparated fluid component (820) subsequent to being removed via bowlchamber (740A).
 27. The apparatus of claim 26 further comprising means(606) to reinfuse treated second separated fluid component (820) andsaid first separated fluid component (810) back into said source (600),wherein said apparatus is a closed-loop apparatus when connected to saidsource (600).
 28. The apparatus of claim 27 wherein said reinfusionmeans (606) comprises a needle or catheter.
 29. The apparatus of claim26 further comprising an anticoagulant source (615) fluidly connectedbetween said means (605) to remove said fluid (800) from said source(600) and said first bowl channel (420A).
 30. The apparatus of claim 26wherein said means (605) to remove said fluid (800) from said source(600) comprises a needle or catheter (605).
 31. The apparatus of claim26 wherein said means (607) to remove said first separated fluidcomponent (810) comprises a pump (617).
 32. The apparatus of claim 26wherein said treatment means (609) comprises a chamber and a source ofultraviolet radiation.
 33. A connection sleeve (500A) for fluidlyconnecting an external conduit (20A) having a first conduit channel(780A) to a lumen (400A) of the centrifuge bowl (10A) having a firstbowl channel (420A), said connection sleeve (500A) comprising; a body(830A) having an upper sleeve end (831A) and a lower sleeve end (832A),said lower sleeve end (832A) adapted to be secured to said centrifugebowl (10A); and a sleeve wall (835A) adapted to receive and hold saidexternal conduit (20A); said sleeve wall (835A) reinforced by one tofour sleeve rings (833A); a sleeve flange (790A) on said lower sleeveend (832A), said sleeve flange (790A) having a bottom surface (847A) andencircling a lumen mounting recess (851A) adapted to engage a lumenconnector (481A) and outer housing outlet (700A) of said centrifuge bowl(10A).
 34. The connection sleeve (500A) of claim 33 wherein said bottomsurface (847A) further comprises protrusions (843A) for engaging lumenconnector (481A).
 35. The connection sleeve (500A) of claim 33 whereinsaid connection sleeve (500A) is adapted to be overmolded to saidexternal conduit (20A).
 36. The connection sleeve (500A) of claim 33wherein said connection sleeve (500A) is made of a same material asexternal conduit (20A).
 37. The connection sleeve (500A) of claim 33wherein said lumen mounting recess (851A) and the top surface (482A) oflumen connector (481A)
 38. An anchor sleeve (870A) for securing anexternal conduit (20A) having conduit channels (760A, 770A, 780A) to arestraint (918A), said anchor sleeve (870A) comprising: a body (870A)having a first anchor end (873A) and a second anchor end (874A); aplurality of longitudinal ribs (877A) in parallel with said conduitchannels, said longitudinal ribs having first rib ends (877B) and secondrib ends (877C) said second rib ends (877C) extending beyond the firstanchor end (873A).
 39. An anchor sleeve of claim 38 wherein the numberof longitudinal ribs is three.
 40. A conduit assembly (860A) for fluidlyconnecting a source (600) of fluid (800) to a centrifuge bowl (10A)comprising: an external conduit (20A) of approximately constant diameterhaving a first conduit end (861A) and a second conduit end (862A); aconnection sleeve (500A) secured to said first conduit end (861A), saidconnection sleeve (500A) adapted to fluidly connect to said centrifugebowl (10A); an anchor sleeve (870A) secured to said second conduit end(862A); a first bearing ring (871A) surrounding said external conduit(20A) and positioned between said connection sleeve (500A) and saidanchor sleeve (870A), said first bearing ring (871A) adapted to engage ameans (900) for rotating said centrifuge bowl (10A); and a firstassembly channel (990A), a second assembly channel (991A), and a thirdassembly channel (992A) extending through said conduit assembly (860A).41. The conduit assembly (860A) of claim 40 wherein said connectionsleeve (500A) and said anchor sleeve (870A) are overmolded to saidexternal conduit (20A).
 42. The conduit assembly (860A) of claim 40wherein: said anchor sleeve (870A) has a first anchor end (873A) and asecond anchor end (874A), said first anchor end (873A) being secured tosaid external conduit (20A), said anchor sleeve (870A) increasing indiameter from said first anchor end (873A) to said second anchor end(874A); said connection sleeve (500A) has an upper sleeve end (831A) anda lower sleeve end (832A), said upper sleeve end (831A) being secured tosaid external conduit (20A), said connection sleeve (500A) increasing indiameter from said upper sleeve end (831A) to said lower sleeve end(832A); and said anchor sleeve (870A), connection sleeve (500A), andexternal conduit (20A) are made of the composition.
 43. The conduitassembly (860A) of claim 40 wherein said connection sleeve (500A)comprises a sleeve flange (790A).
 44. The conduit assembly (860A) ofclaim 40 further comprising a second bearing ring (872A) surroundingsaid conduit (20A) and positioned between said first bearing ring (871A)and said anchor sleeve (870A), said second bearing ring (872A) adaptedto engage a means (900) for rotating said centrifuge bowl (10A).
 45. Theconduit assembly (860A) of claim 40 wherein said first and secondbearing rings (871A, 872A) are 7.5 to 9.5 inches apart.
 46. The conduitassembly (860A) of claim 45 wherein said first bearing ring (871A) is5.0 to 5.5 inches from a lower end (832A) of said connection sleeve(500A).
 47. A method for separating components of a fluid (800)comprising a higher density component (810) and a lower densitycomponent (820), the method comprising: providing a centrifuge bowl(10A) comprising a first bowl channel (420A), a second bowl channel(410A), and a bowl chamber (740A); flowing said fluid (800) from asource (600) into said centrifuge bowl (10A) through said first bowlchannel (420A); rotating said centrifuge bowl (10A) about an axis (11);removing said higher density component (810) from said bowl (10A) viasaid second bowl channel (410A); and removing said lower densitycomponent (820) from said bowl (10A) via said bowl chamber (740A). 48.The method of claim 47 wherein said centrifuge bowl (10) furthercomprises: an outer housing (100A) with an upper housing end (110A) anda lower housing end (190A), wherein said outer housing (100A) increasesin diameter from said upper housing end (110A) to said lower housing end(190A), said lower housing end (190A) having a housing floor (180A) andsaid housing upper end (110A) having a housing outlet (700A), said outerhousing (100A) having an interior volume (710A) and adapted for rotationabout a center axis (11); a top core (200A) having an outer wall (210A),an upper top core end (205A), and a lower top core end (295A); said topcore (200A) connected with said outer housing (100A) for rotationtherewith; occupying a top coaxial volume of said interior volume (710A)of said outer housing (100A); and providing a top separation volume(220A) between said top core (200A) and said outer housing (100A); saidupper top core end (205A) having a lumen connector (481A); said lumenconnector (481A) having a first lumen wall (401 A) extending downwardfrom the a top surface (482A) of the lumen connector (481A); said lumenconnector (481A) further having an inner lumen wall (325A) within saidfirst lumen wall (401A) and extending downward from the top surface(482A); said inner lumen wall having a top wall end (325C) and a bottomwall end (325B); an upper plate (299A) having a top surface (298A), abottom surface (297A), a second lumen wall (402A) extending above saidtop surface (298A); said upper plate (299A) having a circumferenceadapted to form a tight fit with the lower top core end (295A) forrotation therewith; said second lumen wall (402A) adapted to overlapwith said first lumen wall (401A) to form a lumen (400A) having an upperlumen end (480A) and a lower lumen end (490A); said lumen (400A) forminga first bowl channel (420A) for inflowing said fluid (800) and extendingaxially through said core 200A leading to indentation (186A) andtrenches (305A); a bottom core (201A) having an outer wall (211A), a topsurface (309A) contacting and connected with bottom surface (297A) ofupper plate (299A) for rotation therewith; an upper bottom core end(206A), a lower bottom core end (296A), a top surface (309A) having anindentation (186A) and a trench (305A), and a lumen wall (324A) that hasan upper wall end (324C) and a lower wall end (324B); said bottom coreoccupying a bottom coaxial volume of said interior volume (710A) of saidouter housing (100A) and providing a bottom separation volume (220B)between said bottom core (201B) and said outer housing (100A); saidupper wall end (324C) of lumen wall (324A) is adapted to engage withbottom wall end (325B) of inner lumen wall (325A) to form a second bowlchannel (410A) for removing a first separated fluid component (810);said top surface (309A) is adapted to engage with the bottom surface297A of the upper plate (299A); a lower plate (300A) having a topsurface (730A), a bottom surface (730B), and a hollow cylinder (320A)near center of lower plate (300A); said hollow cylinder (320A) has anopening (302A) adapted to engage with lower wall end (324B) of lumen(324A); and said lower plate (300A) having a circumference adapted toform a tight fit with the lower bottom core end (296A) for rotationtherewith; a connection sleeve (500A) having a sleeve flange (790A)surrounding a lumen mounting recess (851A); said lumen mounting recess(851A) and top surface (482A) of lumen connector (481A) engaged to formthe bowl chamber (740A) for removing a second separated fluid component(820); said connection sleeve (500A) further adapted to be secured tosaid apparatus (10A) near said housing outlet (700A) of said outerhousing (100A) for rotation therewith.
 49. The method of claim 47wherein said step of removing said first separated fluid component (810)comprises applying negative pressure to said second bowl channel (410A).50. The method of claim 47 wherein said negative pressure is applied bya pump (617).
 51. The method of claim 50 wherein said pump (617)provides substantially stable flow.
 52. The method of claim 47 whereinsaid step of removing said first separated fluid component (810)comprises applying positive pressure to said centrifuge bowl (10A). 53.The method of claim 47 wherein said fluid (800) comprises a biologicalfluid.
 54. The method of claim 53 wherein said biological fluidcomprises blood.
 55. The method of claim 54 wherein said higher densitycomponent (810) comprises red blood cells and said lower densitycomponent (820) comprises a buffy coat.
 56. The method of claim 55further comprising the step of collecting platelets from said lowerdensity component (820).
 57. The method of claim 55 further comprisingthe step of reinfusing said higher density component (810) into saidsource (600).
 58. The method of claim 55 further comprising: treatingsaid lower density component (820); and reinfusing said treated lowerdensity component (820) into said source (600) to treat, ameliorate,prevent, or delay the onset of white blood cell or T-cell mediateddiseases.
 59. The method of claim 58 wherein said method is completed inless than 70 minutes.
 60. The method of claim 58 wherein said whiteblood cell and T-cell mediated diseases are selected from the groupconsisting of cancer, T-cell lymphoma, Graft-versus-Host disease,Rheumatoid Arthritis, Progressive Systematic Sclerosis, Juvenile OnsetDiabetes, Inflamatory Bowel Disease, Alopecia Areata, AnkylosingSpondylitis, Antiphospholipid Syndrome, Autoimmune Addison's Disease,Autoimmune Hemolytic Anemia, Autoimmune Hepatitis, Behcet's Disease,Bullous Pemphigoid, Cardiomyopathy, Celiac Sprue-Dermatitis, ChronicFatigue Immune Dysfunction Syndrome, Chronic Inflammatory DemyelinatingPolyneuropathy, Churg-Strauss Syndrome, Cicatricial Pemphigoid, CRESTSyndrome, Cold Agglutinin Disease, Crohn's Disease, Discoid Lupus,Essential Mixed Cryoglobulinemia, Fibromyalgia-Fibromyositis, Graves'Disease, Guillain-Barré Syndrome, Hashimoto's Thyroiditis, IdiopathicPulmonary Fibrosis, Idiopathic Thrombocytopenia Purpura, IgANephropathy, Insulin Dependent Diabetes, Juvenile Arthritis, LichenPlanus, Ménière's Disease, Mixed Connective Tissue Disease, MultipleSclerosis, Myasthenia Gravis, Pemphigus Vulgaris, Pernicious Anemia,Polyarteritis Nodosa, Polychondritis, Polyglandular Syndromes,Polymyalgia Rheumatica, Polymyositis and Dermatomyositis, PrimaryAgammaglobulinemia, Primary Biliary Cirrhosis, Psoriasis, Raynaud'sPhenomenon, Reiter's Syndrome, Rheumatic Fever, Rheumatoid Arthritis,Sarcoidosis, Scleroderma, Sjögren's Syndrome, Stiff-Man Syndrome,Systematic Lupus Erythematosus, Takayasu Arteritis, TemporalArteritis/Giant Cell Arteritis, Ulcerative Colitis, Uveitis, Vasculitis,Vitiligo, and Wegener's Granulomatosis.
 61. The method of claim 58further comprising ameliorating or preventing organ or tissue transplantrejection.
 62. The system of claim 58 wherein said treatment stepcomprises irradiating said lower density component (820).
 63. The methodof claim 58 wherein said treatment step is performed so as to induceapoptosis within said lower density component (820).
 64. The method ofclaim 58 wherein said method is performed continuously without the needto batch process said fluid (800).